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Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis
Open accessAbstract
Microglia are the resident brain macrophages and they have been traditionally studied as orchestrators of the brain inflammatory response during infections and disease. In addition, microglia has a more benign, less explored role as the brain professional phagocytes. Phagocytosis is a term coined from the Greek to describe the receptor-mediated engulfment and degradation of dead cells and microbes. In addition, microglia phagocytoses brain-specific cargo, such as axonal and myelin debris in spinal cord injury or multiple sclerosis, amyloid-β deposits in Alzheimer's disease, and supernumerary synapses in postnatal development. Common mechanisms of recognition, engulfment, and degradation of the different types of cargo are assumed, but very little is known about the shared and specific molecules involved in the phagocytosis of each target by microglia. More importantly, the functional consequences of microglial phagocytosis remain largely unexplored. Overall, phagocytosis is considered a beneficial phenomenon, since it eliminates dead cells and induces an anti-inflammatory response. However, phagocytosis can also activate the respiratory burst, which produces toxic reactive oxygen species (ROS). Phagocytosis has been traditionally studied in pathological conditions, leading to the assumption that microglia have to be activated in order to become efficient phagocytes. Recent data, however, has shown that unchallenged microglia phagocytose apoptotic cells during development and in adult neurogenic niches, suggesting an overlooked role in brain remodeling throughout the normal lifespan. The present review will summarize the current state of the literature regarding the role of microglial phagocytosis in maintaining tissue homeostasis in health as in disease.
Overview
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TL;DR
This review argues that microglial phagocytosis is Janus-faced: it clears apoptotic cells, synapses, myelin/axonal debris, and pathogens to maintain brain homeostasis, but can also trigger respiratory burst, inflammation, or kill live neurons. It synthesizes receptor mechanisms and physiological/pathological roles while emphasizing that in vivo consequences and quantification remain largely unresolved.
Key findings
- Microglia are yolk sac-derived brain macrophages that phagocytose apoptotic cells, supernumerary synapses, axonal and myelin debris, amyloid-β (Aβ), and microorganisms; in physiological conditions, unchallenged/ramified microglia are efficient phagocytes, challenging the assumption that they must be preactivated to phagocytose.
- Phagocytic clearance is rapid: in vitro microglial clearance of an apoptotic cell is 25–95 min; in vivo clearance is estimated at 70–90 min, consistent with a general 1–2 h macrophage clearance time. During development, microglia phagocytose 97% of apoptotic cells in the fimbria (E18), 88% and 100% in hippocampal CA (E16 and P0), 18% and 86% in cerebral cortex (E16 and P0), and 93% in dentate gyrus (P0); in adult dentate gyrus from 1–12 months, >90%; but only 50% at peak cell death (P3) in developing cerebellum.
- Consequences can be beneficial or detrimental: apoptotic-cell phagocytosis is largely anti-inflammatory and can promote neuronal survival/neurogenesis, while phagocytosis can activate NADPH oxidase/respiratory burst producing reactive oxygen species; under inflammatory conditions, microglial phagocytosis can kill viable neurons (“phagoptosis”), e.g., via TLR2/TLR4, peroxynitrite, MFG-E8, and vitronectin receptor.
- In disease, microglial phagocytosis is context-dependent: bacteria injected into the corpus callosum of early postnatal rats are engulfed in large numbers 1–3 h after injection and completely eliminated in 24 h, though phagosomes persist up to 7 days; Aβ plaques are not clearly phagocytosed in vivo; CNS myelin debris clearance is inefficient and can be increased by LPS without axonal regeneration.
Methods
- Design: narrative review; no primary experiments. It synthesizes current literature on microglial phagocytosis in health and disease.
- Data/sample: referenced studies include in vitro microglial/macrophage cultures, co-cultures, mouse models (development, EAE/MS, Rett syndrome, Alzheimer’s disease, prion disease, Parkinson’s disease, stroke, glioma), human patient samples, and C. elegans live imaging; includes Table 1 of receptors and Figures 1–4.
- Main analysis: conceptual synthesis organized around the three-step model (find-me, eat-me, digest-me), functional consequences (antigen presentation, respiratory burst, inflammatory modulation), and target-specific sections (spines, apoptotic cells, pathogens, tumor cells, Aβ, myelin/axonal debris).
Limitations
- Stated: most studies assess microglial phagocytosis exclusively in vitro; lack of molecular tools to specifically block recognition, engulfment, and degradation has precluded understanding the global impact of microglial phagocytosis in vivo; many in vivo experiments rely on phagocytosis markers such as CD68/ED1 whose function is unknown; few studies quantify microglial phagocytosis in vivo, and many rely on qualitative observation.
- Stated: basic phagocytic mechanisms are extrapolated from bone marrow-derived tissue macrophages to yolk sac-derived microglia, but these assumed similarities might not fully hold true.
- Evident: as a review, it does not provide new primary data or a systematic meta-analysis; many conclusions about in vivo consequences, especially anti-inflammatory effects and Aβ clearance, are described as unresolved or controversial.
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In the paper
“However, a higher expression of ED1 seems to correlate with the capacity of postnatal microglia to engulf synapses (Schafer et al., 2012).”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > Definition of phagocytosis
What the sources say
- Not checked yetcites Schafer et al., 2012
Strength:hedged· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“Microglial processes are highly motile (Davalos et al., 2005; Nimmerjahn et al., 2005)”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > The mechanics of phagocytosis > Find-me
What the sources say
- Not checked yetcites Davalos et al., 2005
- Not checked yetcites Nimmerjahn et al., 2005
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“and macrophages from mice deficient in CD68 have no defects in phagocytosis of bacteria (Song et al., 2011).”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > Definition of phagocytosis
What the sources say
- Not checked yetcites Song et al., 2011
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“In addition, apoptotic cells can release signals to attract macrophages and DCs, such as the extracellular nucleotides ATP and UTP (Elliott et al., 2009).”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > The mechanics of phagocytosis > Find-me
What the sources say
- Not checked yetcites Elliott et al., 2009
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“In vitro, live imaging has determined that the clearance time to completely eliminate an apoptotic cell by microglia is 25–95 min in a co-culture system (Parnaik et al., 2000)”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > Definition of phagocytosis
What the sources say
- Not checked yetcites Parnaik et al., 2000
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In the paper
“Furthermore, few studies have attempted to quantify the extent of microglial phagocytosis in vivo (Ashwell, 1990; Dalmau et al., 2003; Parnaik et al., 2000; Sierra et al., 2010)”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > Definition of phagocytosis
What the sources say
- Not checked yetcites Ashwell, 1990
- Not checked yetcites Dalmau et al., 2003
- Not checked yetcites Parnaik et al., 2000
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“These numbers are in agreement with a general 1–2 h clearance time for macrophages (Henson and Hume, 2006).”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > Definition of phagocytosis
What the sources say
- Not checked yetcites Henson and Hume, 2006
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesThe paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“One major problem is that the function of CD68 is unknown.”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > Definition of phagocytosis
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, the number of apoptotic cells observed in particular time point represents only a small fraction of the actual number of apoptotic cells generated (or total number of cells which disappear).”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > Definition of phagocytosis
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“in vivo, the microglial clearance time of apoptotic cells in physiological conditions has been estimated to be 70–90 min (Sierra et al., 2010).”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > Definition of phagocytosis
What the sources say
- Not checked yetcites Sierra et al., 2010
Strength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
- Probably not a substantial claim. 37
- It may state two separate claims as one. 54
- The quote only partly states this claim. 1
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In the paper
“Microglia are yolk sac-derived, invade the brain during early embryonic development and then locally proliferate in the brain (Ginhoux et al., 2010; Schulz et al., 2012).”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > Definition of phagocytosis
What the sources say
- Not checked yetcites Ginhoux et al., 2010
- Not checked yetcites Schulz et al., 2012
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“To further complicate the issue, macrophage phagocytosis has two main targets: dead resident cells (apoptotic or necrotic) and live invading microorganisms; whereas microglial phagocytosis appears to be adapted to the brain environment for remodeling tasks such as engulfment of synapses, axonal and myelin debris, or clearance of proteins with very high turnover such as amyloid beta (Aβ) protein.”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > Definition of phagocytosis
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Similarly, microglial phagocytosis of axonal or myelin debris can be quantified using confocal microscopy to determine the percentage of microglia containing neurofilament-positive axonal material (Hosmane et al., 2012) or myelin basic protein (MBP) (Nielsen et al., 2009).”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > Definition of phagocytosis
What the sources say
- Not checked yetcites Hosmane et al., 2012
- Not checked yetcites Nielsen et al., 2009
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Similar in size (0.5 μm in diameter) and purpose (close cell–cell contact) to its immunological and neural counterparts, phagocytic synapses are specialized regions of the membrane where the apoptotic cell and the phagocyte interact through microclusters of receptors.”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > The mechanics of phagocytosis > Eat-me
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“To further complicate the issue, macrophage phagocytosis has two main targets: dead resident cells (apoptotic or necrotic) and live invading microorganisms; whereas microglial phagocytosis appears to be adapted to the brain environment for remodeling tasks such as engulfment of synapses, axonal and myelin debris, or clearance of proteins with very high turnover such as amyloid beta (Aβ) protein.”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > Definition of phagocytosis
Strength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✗ Based: failsProbably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Detection of pathogen-associated molecular patterns (PAMPS) is mediated through scavenger receptors in conjunction with Toll-like receptors (TLRs) such as the CD14/TLR4 complex, or receptors of the immunoglobulin superfamily (e.g., c-type lectins).”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > The mechanics of phagocytosis > Eat-me
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“More recently, a similar parameter was described to quantify microglial phagocytosis of synaptic inputs (allegedly, presynaptic terminals) using high resolution confocal microscopy and three-dimensional rendering to estimate the volume of internalized inputs over the total volume of microglia (Schafer et al., 2012).”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > Definition of phagocytosis
What the sources say
- Not checked yetcites Schafer et al., 2012
Strength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“and many rely on a qualitative observation of microglial engulfment to determine whether microglia is phagocytosing or not.”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > Definition of phagocytosis
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Antibodies such as IgG and proteins of the complement system such as C3b, bind to phagocyte Fc receptors and complement receptor 3 (CR3), respectively, and mediate phagocytosis (Underhill and Goodridge, 2012).”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > The mechanics of phagocytosis > Eat-me
What the sources say
- Not checked yetcites Underhill and Goodridge, 2012
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Hsp60 is exposed in the surface of apoptotic cells (Goh et al., 2011) and increases the phagocytic activity of microglia (Stefano et al., 2009).”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > The mechanics of phagocytosis > Eat-me
What the sources say
- Not checked yetcites Goh et al., 2011
- Not checked yetcites Stefano et al., 2009
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Several candidates have been proposed, namely, anionic oligosaccharides such as bacterial lipopolysaccharides (Daws et al., 2003; Quan et al., 2008) and heat shock protein 60 (Hsp60) (Stefano et al., 2009).”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > The mechanics of phagocytosis > Eat-me
What the sources say
- Not checked yetcites Daws et al., 2003
- Not checked yetcites Quan et al., 2008
- Not checked yetcites Stefano et al., 2009
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“These receptors and their targets closely interact in what has been termed “engulfment synapse” or “phagocytic synapse” (Ravichandran, 2010; Dustin, 2012; Underhill and Goodridge, 2012).”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > The mechanics of phagocytosis > Eat-me
What the sources say
- Not checked yetcites Ravichandran, 2010
- Not checked yetcites Dustin, 2012
- Not checked yetcites Underhill and Goodridge, 2012
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“however its ligand in apoptotic cells remains elusive.”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > The mechanics of phagocytosis > Eat-me
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The phagocytosis of smaller particles (synapses, axons, protein aggregates) is likely to be even faster.”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > Definition of phagocytosis
Strength:hedged· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✗ Based: failsProbably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
In the paper
“Our current understanding of the mechanical process of phagocytosis is summarized in the three-step model: find-me, eat-me, and digest-me (Savill et al., 2002), which addresses the engulfment and degradation of apoptotic cells and microorganisms by macrophages and DCs.”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > The mechanics of phagocytosis
What the sources say
- Not checked yetcites Savill et al., 2002
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Some of these receptors serve to tether the phagocyte and the target together; others actually trigger internalization (Underhill and Goodridge, 2012).”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > The mechanics of phagocytosis > Eat-me
What the sources say
- Not checked yetcites Underhill and Goodridge, 2012
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“Like the immunological synapse formed between antigen presenting cells (APCs) and T lymphocytes, and in contrast to the synapses formed between neurons, phagocytic synapses are short-lived and last only a few minutes (Dustin, 2012).”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > The mechanics of phagocytosis > Eat-me
What the sources say
- Not checked yetcites Dustin, 2012
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Microglia express the fractalkine receptor (CX3CR1), which promotes phagocytosis of apoptotic cells (Noda et al., 2011) but shifts microglia toward a phenotype with less capacity to phagocytose Aβ (Lee et al., 2010; Liu et al., 2010).”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > The mechanics of phagocytosis > Find-me
What the sources say
- Not checked yetcites Noda et al., 2011
- Not checked yetcites Lee et al., 2010
- Not checked yetcites Liu et al., 2010
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“In the adult hippocampus, the expression of ED1 in microglia phagocytosing apoptotic cells is similar to non-phagocytic microglia and much lower than the expression induced by inflammatory challenge (Sierra et al., 2010).”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > Definition of phagocytosis
What the sources say
- Not checked yetcites Sierra et al., 2010
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Phagocytic synapses are also characterized by exclusion of phosphatases (Dustin, 2012)”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > The mechanics of phagocytosis > Eat-me
What the sources say
- Not checked yetcites Dustin, 2012
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“TREM2 is known to interact with the signaling adapter protein named DNAX-activation protein of 12 kD (DAP12) (Paloneva et al., 2002)”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > The mechanics of phagocytosis > Eat-me
What the sources say
- Not checked yetcites Paloneva et al., 2002
Strength:boosted· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“While it is likely that microglia utilizes similar mechanisms, direct evidence of the molecular details of these events in microglia, beyond the receptors involved in the recognition of the targets, is largely missing.”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > The mechanics of phagocytosis
Strength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✗ Based: failsProbably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
- The authors state this as an assumption: Basic phagocytic mechanisms from bone marrow-derived tissue macrophages can be extrapolated to microglia.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“In addition, whether phagocytosis impacts proliferation, survival, or differentiation of the phagocyte remains unexplored.”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > Functional consequences of phagocytosis
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✗ Based: failsProbably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
In the paper
“a member of the Src family whose deficiency impairs macrophage phagocytosis (Lowell et al., 1994).”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > The mechanics of phagocytosis > Eat-me
What the sources say
- Not checked yetcites Lowell et al., 1994
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Phagocytosis triggers activation of several intracellular signaling pathways and remodels the cytoskeleton and cell membrane (Lee et al., 2007).”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > Functional consequences of phagocytosis
What the sources say
- Not checked yetcites Lee et al., 2007
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The phagocytic cup closes and thus forms the phagosome around the target.”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > The mechanics of phagocytosis > Digest-me
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Of the complex process of signal transduction and formation of the phagocytic cup, very little is known in microglia.”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > The mechanics of phagocytosis > Eat-me
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“ELMO-1 function is regulated by phosphorylation by the hematopoietic cell kinase (HCK) (Yokoyama et al., 2005)”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > The mechanics of phagocytosis > Eat-me
What the sources say
- Not checked yetcites Yokoyama et al., 2005
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“These data suggest that a failure in microglial phagocytosis does not underlie the pathology of the Rett syndrome but, nonetheless, increasing phagocytosis may be beneficial (Derecki et al., 2012).”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > The mechanics of phagocytosis > Digest-me
What the sources say
- Not checked yetcites Derecki et al., 2012
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Again, the process of phagosome formation and cargo degradation has been barely addressed in microglia.”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > The mechanics of phagocytosis > Digest-me
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“When administered systemically, annexin V reaches the brain and, as expected, leads to accumulation of apoptotic debris, although it has not been quantified whether it actually prevents phagocytosis (Lu et al., 2011).”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > The mechanics of phagocytosis > Digest-me
What the sources say
- Not checked yetcites Lu et al., 2011
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“While Rett syndrome is mostly considered a primary neuronal disease, defects in phagocytosis and inflammatory response are found in Mecp2-deficient microglia (Derecki et al., 2012).”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > The mechanics of phagocytosis > Digest-me
What the sources say
- Not checked yetcites Derecki et al., 2012
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Interestingly, the disease is mimicked by microglial-specific depletion of Mecp2 and phagocytosis is blocked by intravenous injection of annexin V, but not by either manipulation independently.”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > The mechanics of phagocytosis > Digest-me
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“These phagolysosomes contain hundreds of proteins, including hydrolases such as cathepsins to digest the target; and proton pumps such as vacuolar ATPases to acidify the medium (Garin et al., 2001).”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > The mechanics of phagocytosis > Digest-me
What the sources say
- Not checked yetcites Garin et al., 2001
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Enhancing brain phagocytosis via intravenous delivery of TREM2-transduced bone marrow-derived precursor cells potentiates the clearance of degenerated myelin, decreases the inflammatory response and ameliorates the course of the disease in the mouse model of multiple sclerosis (MS), experimental acute encephalomyelitis (EAE) (Takahashi et al., 2007).”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > The mechanics of phagocytosis > Digest-me
What the sources say
- Not checked yetcites Takahashi et al., 2007
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Further, bone marrow cells transplanted into irradiated Rett mice differentiate into microglia and partially arrest the pathology of the disease (Derecki et al., 2012).”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > The mechanics of phagocytosis > Digest-me
What the sources say
- Not checked yetcites Derecki et al., 2012
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Treatment with annexin V impaires the generation of newborn neurons in adult neurogenic niches without affecting the proliferation of neuronal precursors, suggesting that phagocytosis is important for the differentiation and/or survival of the newborn cells (Lu et al., 2011).”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > The mechanics of phagocytosis > Digest-me
What the sources say
- Not checked yetcites Lu et al., 2011
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“An emerging pivotal complex is that formed by ELMO-1 and dedicator of cytokinesis 180 (DOCK-180), which is activated among other receptors by BAI-1 and act as a guanine nucleotide exchange factor for Rac (Park et al., 2008; Patel et al., 2011).”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > The mechanics of phagocytosis > Eat-me
What the sources say
- Not checked yetcites Park et al., 2008
- Not checked yetcites Patel et al., 2011
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“the location where the actual degradation occur remains unexplored.”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > The mechanics of phagocytosis > Digest-me
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“To execute the degradation of the target, phagosomes go through a process of maturation in which they fuse sequentially with early and late endosomes, and lysosomes, to form phagolysosomes (Desjardins et al., 1994).”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > The mechanics of phagocytosis > Digest-me
What the sources say
- Not checked yetcites Desjardins et al., 1994
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“A method recently proposed is the use of annexin V, a PS binding protein, to block phagocytosis.”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > The mechanics of phagocytosis > Digest-me
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Aβ plaques cause physical damage of the neural tissue and lead to functional deficits if they are not removed (Wang et al., 2011)”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > The mechanics of phagocytosis > Digest-me
What the sources say
- Not checked yetcites Wang et al., 2011
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“In contrast, three major functional consequences of microglial phagocytosis have been well-described: antigen presentation, activation of the respiratory burst, and modulation of inflammatory responses.”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > Functional consequences of phagocytosis
Strength:boosted· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✗ Based: failsProbably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Clearance of microbes or debris is a direct intervention of microglia to remove invading pathogens or to clean up the tissue from unwanted material.”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > Functional consequences of phagocytosis
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“In microglia, the respiratory burst is triggered by hypoxia/reoxygenation (Spranger et al., 1998) and LPS (Qin et al., 2004) and results in the extracellular release of ROS.”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > Functional consequences of phagocytosis > Respiratory burst
What the sources say
- Not checked yetcites Spranger et al., 1998
- Not checked yetcites Qin et al., 2004
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“The M1 phenotype is basically neurotoxic, while the M2 phenotype is more neuroprotective (Durafourt et al., 2012).”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > Microglial phagocytosis in physiological conditions
What the sources say
- Not checked yetcites Durafourt et al., 2012
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The high efficiency of phagocytosis, that is, the high coupling between apoptosis and phagocytosis, has also suggested the idea that phagocytosis executes the final stages of apoptotic cell death.”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > Microglial phagocytosis in physiological conditions > Microglial phagocytosis of apoptotic cells during brain development and in neurogenic niches
Strength:hedged· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“More recently it has been described that the immunosuppression induced by phagocytosis of apoptotic cells depends on the presence of the complement protein C1q bound to apoptotic cells, without which phagocytosis is pro-inflammatory (Fraser et al., 2010).”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > Functional consequences of phagocytosis > Modulation of inflammatory responses
What the sources say
- Not checked yetcites Fraser et al., 2010
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Similarly, phagocytosis of an apoptotic neuronal line induces an increased production of TGFβ and neural growth factor (NGF) in basal conditions; as well as a decreased production of TNFα, nitrite, and prostaglandin E2 during LPS challenge in vitro (De Simone et al., 2003).”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > Functional consequences of phagocytosis > Modulation of inflammatory responses
What the sources say
- Not checked yetcites De Simone et al., 2003
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Non-professional phagocytes such as astrocytes delay phagocytosis for several hours (Parnaik et al., 2000) and engulf with much lower capacity (Magnus et al., 2002), at least in vitro.”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > Microglial phagocytosis in physiological conditions > Microglial phagocytosis of apoptotic cells during brain development and in neurogenic niches
What the sources say
- Not checked yetcites Parnaik et al., 2000
- Not checked yetcites Magnus et al., 2002
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: Microglia are the professional brain phagocytes.
In the paper
“In MECP2-deficient mice, a model of Rett syndrome, microglia has defective phagocytosis in vitro, and preventing phagocytosis in the mice exacerbates the symptoms (Derecki et al., 2012).”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > Microglial phagocytosis in physiological conditions > Microglial phagocytosis of spines
What the sources say
- Not checked yetcites Derecki et al., 2012
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“In fact, antigen presentation in the CNS is thought to occur not in the parenchyma, but in the meninges and choroid plexus, which contain perivascular APCs, or by direct drainage of CNS antigens in the cerebrospinal fluid from the subarachnoidal space to channels in the cribiform plate and ultimately into deep cervical lymph nodes (Galea et al., 2007; Ransohoff and Engelhardt, 2012).”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > Functional consequences of phagocytosis > Antigen presentation
What the sources say
- Not checked yetcites Galea et al., 2007
- Not checked yetcites Ransohoff and Engelhardt, 2012
Strength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“but microglia do fail to phagocytose prion protein (PrPSc), which accumulates in the brain and leads to neurodegeneration (Hughes et al., 2010).”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > Microglial phagocytosis in pathological conditions > Microglial phagocytosis of dead cells in pathological conditions
What the sources say
- Not checked yetcites Hughes et al., 2010
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“For instance, E. coli bacteria injected into the corpus callosum of early postnatal rats are engulfed in large numbers 1–3 h after injection, and are completely eliminated in 24 h (Kaur et al., 2004).”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > Microglial phagocytosis in pathological conditions > Microglial phagocytosis of invading microorganisms
What the sources say
- Not checked yetcites Kaur et al., 2004
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“Contrary to apoptosis, necrosis is characterized by bursting of the cell membrane and spillover of cellular contents (Savill et al., 2002).”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > Microglial phagocytosis in pathological conditions > Microglial phagocytosis of dead cells in pathological conditions
What the sources say
- Not checked yetcites Savill et al., 2002
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Further, in inflammatory conditions driven by activation of TLR2 or TLR4, microglial phagocytosis induces cerebellar granule cell death by a complex mechanism involving the microglial release of peroxynitrite which leads to a transient exposure of PS in the neurons and opsonization with MFG-E8, followed by recognition through the vitronectin receptor and phagocytosis by microglia in vitro (Neher”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > Microglial phagocytosis in physiological conditions > Microglial phagocytosis of apoptotic cells during brain development and in neurogenic niches
What the sources say
- Not checked yetcites Neher et al., 2011
- Not checked yetcites Fricker et al., 2012
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one. The quote only partly states this claim.
In the paper
“Here the phagocytosis of latex beads is prevented by the aggregated form, and enhanced by the monomeric form of alpha synuclein, which are found in the parenchyma and the CSF of parkinsonian patients, respectively (Park et al., 2008).”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > Microglial phagocytosis in pathological conditions > Microglial phagocytosis of dead cells in pathological conditions
What the sources say
- Not checked yetcites Park et al., 2008
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“These data suggest that phagoptosis might be partly responsible for neuronal death induced by Aβ, perhaps providing an explanation for the low numbers of dead neurons found in AD (Neniskyte et al., 2011).”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > Microglial phagocytosis in pathological conditions > Microglial phagocytosis of dead cells in pathological conditions
What the sources say
- Not checked yetcites Neniskyte et al., 2011
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“One alternative mechanism could be the passive release of high mobility group 1 protein (HMGB1) by necrotic cells, which binds to the receptor for advanced glycation end products (RAGE) in phagocytes and triggers inflammation (Scaffidi et al., 2002).”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > Microglial phagocytosis in pathological conditions > Microglial phagocytosis of dead cells in pathological conditions
What the sources say
- Not checked yetcites Scaffidi et al., 2002
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“Tumor-associated microglia and macrophages (TAMs) are found in large numbers in human glioblastoma and have a complex and bidirectional relationship with glioma cells which has been reviewed in detail elsewhere (Watters et al., 2005).”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > Microglial phagocytosis in pathological conditions > Microglial phagocytosis of tumor cells
What the sources say
- Not checked yetcites Watters et al., 2005
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“However, microglial phagocytosis of apoptotic cells in vitro is increased by the pro-inflammatory interferon gamma (IFNγ), but it remains unaltered by TNFβ or TGFβ (Chan et al., 2001).”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > Microglial phagocytosis in pathological conditions > Microglial phagocytosis of dead cells in pathological conditions
What the sources say
- Not checked yetcites Chan et al., 2001
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“In this situation, either depleting microglia, blocking vitronectin receptors, inhibiting cytoskeleton polymerization, or preventing recognition of PS with annexin V, all prevent neuronal death induced by nanomolar Aβ (Neniskyte et al., 2011).”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > Microglial phagocytosis in pathological conditions > Microglial phagocytosis of dead cells in pathological conditions
What the sources say
- Not checked yetcites Neniskyte et al., 2011
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Two main forms have been recognized: accidental necrosis, or cell lysis, by exposure of toxins, physical damage, freezing, etc.; and necrosis-like programmed cell death (PCD), which involves specialized caspase-independent signaling pathways such as the apoptosis-inducing factor (AIF) or cathepsins, and evolves without chromatin condensation (Leist and Jaattela, 2001).”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > Microglial phagocytosis in pathological conditions > Microglial phagocytosis of dead cells in pathological conditions
What the sources say
- Not checked yetcites Leist and Jaattela, 2001
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“We argue that the clearance time for phagoptotic neurons is likely to be longer than for phagocytosed apoptotic neurons, because phagoptotic cells fail to activate caspases and other mechanisms of self-destruction and rely exclusively on microglia for degradation (Brown and Neher, 2012).”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > Microglial phagocytosis in pathological conditions > Microglial phagocytosis of dead cells in pathological conditions
What the sources say
- Not checked yetcites Brown and Neher, 2012
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, phagocytosis represents a wide range of responses, from the mere passive clearing of apoptotic cells and the active execution of final stages of apoptosis during development to the aberrant killing of live, healthy neurons during inflammation.”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > Microglial phagocytosis in physiological conditions > Microglial phagocytosis of apoptotic cells during brain development and in neurogenic niches
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“HIV protease inhibitors either block Aβ degradation or enhance secretion of non-degraded Aβ by macrophages (Lan et al., 2012).”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > Microglial phagocytosis in pathological conditions > Microglial phagocytosis of Aβ deposits
What the sources say
- Not checked yetcites Lan et al., 2012
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“In vitro, inflammatory challenge by LPS, TNFα, IL-1β, or IFNγ inhibits fibrillary Aβ phagocytosis, whereas anti-inflammatory cytokines had no effect (Koenigsknecht-Talboo and Landreth, 2005).”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > Microglial phagocytosis in pathological conditions > Microglial phagocytosis of Aβ deposits
What the sources say
- Not checked yetcites Koenigsknecht-Talboo and Landreth, 2005
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“In a compartmentalized co-culture model where neurons were grown in a chamber and their axons extended in bundles through microchannels, axotomy, or nitric oxide treatment-induced axonal degeneration and microglia rapidly cleared the axonal debris (Hosmane et al., 2012).”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > Microglial phagocytosis in pathological conditions > Microglial phagocytosis of myelin and axonal debris
What the sources say
- Not checked yetcites Hosmane et al., 2012
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Aβ phagocytosis is blocked by the anti-inflammatory celecoxib (Persaud-Sawin et al., 2009), but not by minocyline (Familian et al., 2007).”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > Microglial phagocytosis in pathological conditions > Microglial phagocytosis of Aβ deposits
What the sources say
- Not checked yetcites Persaud-Sawin et al., 2009
- Not checked yetcites Familian et al., 2007
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“The clearance of axonal debris is prevented by blocking TRIF signaling in vitro, and TRIF-deficient mice have a smaller percentage of microglia containing neurofilament-positive axonal material after dorsal root axotomy (Hosmane et al., 2012).”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > Microglial phagocytosis in pathological conditions > Microglial phagocytosis of myelin and axonal debris
What the sources say
- Not checked yetcites Hosmane et al., 2012
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“The blood-brain barrier (BBB) is partially disturbed in AD patients, facilitating the extravasation of circulating monocytes (Lai and McLaurin, 2012).”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > Microglial phagocytosis in pathological conditions > Microglial phagocytosis of Aβ deposits
What the sources say
- Not checked yetcites Lai and McLaurin, 2012
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“The most pathogenic form is Aβ (1–42), which forms fibrils, insoluble aggregates found in amyloid plaques in the brains of AD patients, as well as human immunodeficiency virus (HIV)-associated neurocognitive disorders (Xu and Ikezu, 2009).”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > Microglial phagocytosis in pathological conditions > Microglial phagocytosis of Aβ deposits
What the sources say
- Not checked yetcites Xu and Ikezu, 2009
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“In spinal cord injury, the degeneration of the severed axons through anterograde or Wallerian degeneration (WD) is followed by degradation of myelin and apoptosis of myelinating cells, oligodendrocytes (Crowe et al., 1997).”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > Microglial phagocytosis in pathological conditions > Microglial phagocytosis of myelin and axonal debris
What the sources say
- Not checked yetcites Crowe et al., 1997
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“many tumor cells decrease their sensitivity to apoptosis inducers during oncogenic transformation (Maher et al., 2001)”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > Microglial phagocytosis in pathological conditions > Microglial phagocytosis of tumor cells
What the sources say
- Not checked yetcites Maher et al., 2001
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“in both cases, myelin debris accumulates (Stys et al., 2012)”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > Microglial phagocytosis in pathological conditions > Microglial phagocytosis of myelin and axonal debris
What the sources say
- Not checked yetcites Stys et al., 2012
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“This therapy, while safe, has been proven ineffectual because TAMs clear the viruses away from the tumor (Fulci et al., 2007).”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > Microglial phagocytosis in pathological conditions > Microglial phagocytosis of tumor cells
What the sources say
- Not checked yetcites Fulci et al., 2007
Strength:boosted· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“oncolytic viruses, which selectively replicate in tumor cells, leading to their destruction (Zeyaullah et al., 2012)”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > Microglial phagocytosis in pathological conditions > Microglial phagocytosis of tumor cells
What the sources say
- Not checked yetcites Zeyaullah et al., 2012
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“In both set ups, axonal debris (lacking myelin) had a detrimental effect on axon regrown, which was prevented by microglial phagocytosis (Tanaka et al., 2009; Hosmane et al., 2012)”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > Microglial phagocytosis in pathological conditions > Microglial phagocytosis of myelin and axonal debris
What the sources say
- Not checked yetcites Tanaka et al., 2009; Hosmane et al., 2012
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“microglia from old mutant APP/presenilin 1 mice have a decreased expression of phagocytic genes (SRA, CD36, RAGE, etc.) and increased expression of pro-inflammatory cytokines (TNFα, IL-1β), compared with age-matched wild type mice (Hickman et al., 2008)”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > Microglial phagocytosis in pathological conditions > Microglial phagocytosis of Aβ deposits
What the sources say
- Not checked yetcites Hickman et al., 2008
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Importantly, the size of the plaques remained constant and no evidence of phagocytosis or plaque clearance was obtained (Meyer-Luehmann et al., 2008).”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > Microglial phagocytosis in pathological conditions > Microglial phagocytosis of Aβ deposits
What the sources say
- Not checked yetcites Meyer-Luehmann et al., 2008
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Cultured microglia engulf and partially degrade Aβ in vitro over the first 3 days, but no additional degradation and a slow release of intact Aβ is found afterwards (Chung et al., 1999).”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > Microglial phagocytosis in pathological conditions > Microglial phagocytosis of Aβ deposits
What the sources say
- Not checked yetcites Chung et al., 1999
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“microglial processes and amyloid fibrils were interlaced forming a network, but Aβ was not found within microglia”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > Microglial phagocytosis in pathological conditions > Microglial phagocytosis of Aβ deposits
What the sources say
- Not checked yetcites Stalder et al., 2001
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“this data suggests that the beneficial consequences of enhancing microglial phagocytosis of myelin may be two-fold: clearing myelin and facilitating remyelination.”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > Microglial phagocytosis in pathological conditions > Microglial phagocytosis of myelin and axonal debris
What the sources say
- Not checked yetcites Olah et al., 2012
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In conclusion, microglial phagocytosis is a pivotal mechanism of clearance of cellular debris in health and disease.”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > Conclusion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✗ Based: failsProbably not a substantial claim. The paper may give no reason why it holds.
In the paper
“Microglial phagocytosis of myelin after hemisection of the ascending sensory tract is increased after treating the mice with LPS, resulting in decreased myelin debris, but, unfortunately, no axonal regeneration (Vallieres et al., 2006)”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > Microglial phagocytosis in pathological conditions > Microglial phagocytosis of myelin and axonal debris
What the sources say
- Not checked yetcites Vallieres et al., 2006
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Microglia do phagocytose myelin to some extent in mouse models of MS, a phenomenon which is stimulated by the presence of MBP-reactive T cells (Nielsen et al., 2009).”
§ Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis > Microglial phagocytosis in pathological conditions > Microglial phagocytosis of myelin and axonal debris
What the sources say
- Not checked yetcites Nielsen et al., 2009
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
The authors state this as an assumption.
Basic phagocytic mechanisms from bone marrow-derived tissue macrophages can be extrapolated to microglia.
“In this review we directly extrapolate basic phagocytic mechanisms from bone marrow-derived tissue macrophages to the less-known processes of microglia, but would like to point out that these assumed similarities might not fully hold true to the yolk sac-derived microglia.”
The authors state this as an assumption.
Common mechanisms of recognition, engulfment, and degradation are shared across different types of cargo phagocytosed by microglia.
“Common mechanisms of recognition, engulfment, and degradation of the different types of cargo are assumed, but very little is known about the shared and specific molecules involved in the phagocytosis of each target by microglia.”
The authors state this as an assumption.
Microglial phagocytosis contributes to the maintenance of tissue homeostasis during development and in adult neurogenic niches by rapidly removing cellular debris.
“Assumedly, microglial phagocytosis contributes to the maintenance of tissue homeostasis during development and in adult neurogenic niches by rapidly removing cellular debris.”
The authors state this as an assumption.
Microglial phagocytosis of apoptotic cells in pathological conditions is highly efficient.
“Microglial phagocytosis of apoptotic cells in pathological conditions is assumed to be highly efficient, possibly because of an extrapolation of the physiological phagocytosis during brain development, however this may not be always the case.”
The paper relies on this without support.
Microglia are the professional brain phagocytes.
“Microglia are considered the professional brain phagocytes.”
The authors state this as an assumption.
Expression of phagocytic receptors is triggered by many inflammatory and neurodegenerative paradigms in vivo assumedly inducing an M1 phenotype.
“In addition, expression of phagocytic receptors is triggered by many inflammatory and neurodegenerative paradigms in vivo assumedly inducing an M1 phenotype.”
The authors state this as an assumption.
HMGB1 released during ischemia originates from the necrotic core.
“HMGB1 is also released during ischemia (assumedly, from the necrotic core) in stroke patients and in mice subjected to MCAO”
The authors state this as an assumption.
Apoptosis in AD patients and animal models occurs at low levels over a long period of time.
“death by apoptosis has been documented in AD patients and in animal models of AD, although it is assumed to occur at low levels over a long period of time (Shimohama, 2000)”
The paper relies on this without support.
Inflammation is the main trigger for phagoptosis.
“diseases where inflammation, the main trigger for phagoptosis, occurs”
The paper relies on this without support.
Macrophages and microglia are phenotypically indistinguishable by surface markers.
“macrophages and microglia are phenotypically indistinguishable by surface markers”
The paper relies on this without support.
Experimental interventions such as irradiation of mice lead to invasion of blood-monocytes into the brain parenchyma.
“experimental interventions such as irradiation of mice lead to invasion of blood-monocytes into the brain parenchyma”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“Microglia constantly eliminate cell debris and dead cells through highly efficient phagocytosis using specific recognition, engulfment, and degradation processes to maintain brain homeostasis in health and disease [310,325,326,327].”
From Revisiting the Pathogenesis of X-Linked Adrenoleukodystrophy (2025) · cites this paper as [325]
In the citing paper
“The efficient removal of dying cells is considered an overall anti-inflammatory mechanism, as it prevents further release of cytokines and chemoattractants [76].”
From Risk mitigation of immunogenicity: a key to personalized retinal gene therapy (2021) · cites this paper as [76]
In the citing paper
“Microglia actively clear apoptotic cells, myelin and synaptic debris, axonal fragments and protein deposits from the CNS through phagocytosis [428–430].”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [430]
In the citing paper
“microglial phagocytosis of Aβ deposits in Alzheimer disease models [430,431] requires the autophagy-related factors BECN1, ATG7 and LC3 [432,433].”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [430]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Axonal-debris evidence described as exclusively in vitro despite an in vivo result
MinorThe section says the only available evidence on microglial phagocytosis of axonal debris comes from in vitro models, but it later reports an axotomy experiment in mice measuring microglia containing axonal material.
“The only available data on microglial phagocytosis of axonal debris comes from in vitro models.”
“TRIF-deficient mice have a smaller percentage of microglia containing neurofilament-positive axonal material after dorsal root axotomy (Hosmane et al., 2012).”
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“Over the past 20 years, it has been made clear that the phagocytosis of apoptotic cells is largely anti-inflammatory (Stern et al., 1996; Voll et al., 1997; Fadok et al., 1998).”
Background
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19 of the 266 references couldn’t be matched to a known paper.
Cited by
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Metadata
- Authors
- Sierra, A., Abiega, O., Shahraz, A., & Neumann, H.
- Affiliations
- Ikerbasque (ES)
- University of Bonn (DE)
- Corresponding author
- Sierra, Amanda
- Neumann, Harald
- Venue
- Frontiers in Cellular Neuroscience
- Publisher
- Frontiers Media SA
- Published
- 2013
- Volume
- 7
- Pages
- 6-6
- ISSN
- 1662-5102 (ISSN-L)
- PMC
- PMC3558702
- OpenAlex
- W2136123169
- Cited by
- 574
- References
- 266
- Citations by year
- 2026: 18 · 2025: 30 · 2024: 47 · 2023: 44 · 2022: 48 · 2021: 59 · 2020: 47 · 2019: 52 · 2018: 40 · 2017: 44 · 2016: 38 · 2015: 48 · 2014: 43 · 2013: 15
- FWCI
- 26.53
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Frontiers in Cellular Neuroscience (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Communities in ADDI (Universidad del Pais Vasco) (submittedVersion, cc-by)
- Communities in ADDI (University of the Basque Country) (submittedVersion, other-oa)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Hispana (submittedVersion, other-oa)
- Funders
- Deutsche Forschungsgemeinschaft (KFO177, SFB 704, FOR1336)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Keywords
- microglia, phagocytosis, brain homeostasis, efferocytosis, reactive oxygen species, neuroinflammation, myelin debris, amyloid-beta, synaptic pruning, microglial activation, tissue remodeling
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-06, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-06 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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