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Cited by 107Immune Response and InflammationNeuroinflammation and Neurodegeneration MechanismsInflammasome and immune disorders

Central Role for MyD88 in the Responses of Microglia to Pathogen-Associated Molecular Patterns

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Esen, Nilufer, Kielian, Tammy·2006·The Journal of Immunology
DOI 10.4049/jimmunol.176.11.6802PMC PMC2440502
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Abstract

Microglia, the innate immune effector cells of the CNS parenchyma, express TLR that recognize conserved motifs of microorganisms referred to as pathogen-associated molecular patterns (PAMP). All TLRs identified to date, with the exception of TLR3, use a common adaptor protein, MyD88, to transduce activation signals. Recently, we reported that microglial activation in response to the Gram-positive bacterium Staphylococcus aureus was not completely attenuated following TLR2 ablation, suggesting the involvement of additional receptors. To assess the functional role of alternative TLRs in microglial responses to S. aureus and its cell wall product peptidoglycan as well as the Gram-negative PAMP LPS, we evaluated primary microglia from MyD88 knockout (KO) and wild-type mice. The induction of TNF-α, IL-12 p40, and MIP-2 (CXCL2) expression by S. aureus- and peptidoglycan-stimulated microglia was MyD88 dependent, as revealed by the complete inhibition of cytokine production in MyD88 KO cells. In addition, the expression of additional pattern recognition receptors, including TLR9, pentraxin-3, and lectin-like oxidized LDL receptor-1, was regulated, in part, via a MyD88-dependent manner as demonstrated by the attenuated expression of these receptors in MyD88 KO microglia. Microglial activation was only partially inhibited in LPS-stimulated MyD88 KO cells, suggesting the involvement of MyD88-independent pathways. Collectively, these findings reveal the complex mechanisms for microglia to respond to diverse bacterial pathogens, which occur via both MyD88-dependent and -independent pathways.

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  • BMP9, MyD88, and mTOR were previously involved in restricting amyloidosis, microglial response to pathogens, and pro-inflammatory microglia.

    “which were previously involved in restricting amyloidosis56, microglial response to pathogens57, and pro-inflammatory microglia58”

    From Transcriptional signature in microglia associated with Aβ plaque phagocytosis (2021) · cites this paper as [57]

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Authors
Esen, N., & Kielian, T.
Affiliations
  • Department of Neurobiology and Developmental Sciences, University of Arkansas for Medical Sciences , Little Rock, AR 72205
  • University of Arkansas for Medical Sciences (US)
ORCID
Kielian, Tammy
Venue
The Journal of Immunology
Publisher
Oxford University Press (OUP)
Published
2006-06-01
Volume
176
Issue
11
Pages
6802-6811
ISSN
  • 0022-1767 (ISSN-L)
  • 1550-6606
DOI
10.4049/jimmunol.176.11.6802
PMC
PMC2440502
OpenAlex
W1798758220
Cited by
107
References
1
Citations by year
2026: 4 · 2025: 2 · 2024: 7 · 2023: 5 · 2022: 4 · 2021: 8 · 2020: 3 · 2019: 3 · 2018: 3 · 2017: 3 · 2016: 4 · 2015: 5 · 2014: 5 · 2013: 4 · 2012: 4
FWCI
4.05
Type
journal article
Language
en
Open access
Licence
academic.oup.com/pages/standard-publication-reuse-rights (vor)
Locations
  • The Journal of Immunology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institute of Mental Health (R01 MH65297, R01MH065297)
  • National Institute of Neurological Disorders and Stroke (P30NS047546)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
Keywords
MyD88, microglia, pathogen-associated molecular patterns, Toll-like receptors, Staphylococcus aureus, peptidoglycan, lipopolysaccharide, pattern recognition receptors, TLR9, pentraxin 3, lectin-like oxidized LDL receptor, TNF-α, IL-12p40, CXCL2, MyD88 knockout mice
MeSH terms
Adjuvants, Immunologic, Animals, Cells, Cultured, Enzyme Induction, Lipopolysaccharides, Mice, Inbred C57BL, Peptidoglycan, Staphylococcus aureus, Tumor Necrosis Factor-alpha, Signal Transduction, Microglia, Mice, Knockout, Interleukin-12, Inflammation Mediators, Chemokines, Protein Subunits, Adaptor Proteins, Signal Transducing, Receptors, Pattern Recognition, Mice, Nitric Oxide Synthase Type II, Myeloid Differentiation Factor 88, Interleukin-12 Subunit p40, Chemokine CXCL2

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.

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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