Cited by 123Neuroinflammation and Neurodegeneration MechanismsNeuroscience and Neuropharmacology ResearchInflammasome and immune disorders

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Microglial diversity by responses and responders

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Gertig, Ulla, Hanisch, Uwe-Karsten·2014·Frontiers in Cellular Neuroscience

DOI 10.3389/fncel.2014.00101PMC PMC3978327

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Abstract

Microglia are the principal resident innate immune cells of the CNS. Their contributions to the normal development of the CNS, the maintenance and plasticity of neuronal networks and the safeguarding of proper functionality are becoming more and more evident. Microglia also survey the tissue homeostasis to respond rapidly to exogenous and endogenous threats, primarily with a protective outcome. However, excessive acute activation, chronic activity or an improper adaptation of their functional performance can foster neuropathologies. A key to the versatile response behavior of these cells is their ability to commit to reactive phenotypes, which reveal enormous complexity. Yet the respective profiles of induced genes and installed functions may build up on heterogeneous contributions of cellular subsets. Here, we discuss findings and concepts that consider the variety of microglial activities and response options as being based-at least in part-on a diversity of the engaged cells. Whether it is the production of proinflammatory cytokines, clearance of tissue debris, antigen presentation or the ability to sense neurotransmitters, microglial cells present with an unanticipated heterogeneity of their constitutive and inducible features. While the organizational principles of this heterogeneity are still largely unknown, functional implications are already perceptible.

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Figure 1 Schematic summary of examples indicating microglial response heterogeneity. (A) Stimulation of microglia cells with neurotransmitters and neurohormones triggering calcium signals revealed that only small fractions responded to each compound. Combined stimulation and population analysis thereby suggested an enormous variety in terms of functional receptor expression. (B) Exposure to LPS induced a panpopulational expression of major histocompatibility complex I (MHCI) molecules, indicating that all microglia expressed TLR4. In contrast, only subsets also produced TNFα and/or CCL3. (C) Treatment of microglia with IFNγ caused the expression of major histocompatibility complex II (MHCII) in some but not all cells. On the other hand, MHCII-expressing microglia did not clear myelin-laden exosomes, a function that rather associated with MHCII-negative cells. (D) Exposure of cells to myelin debris resulted in the phagocytic uptake of the material in a subset of microglia. Adapted and expanded from Scheffel et al. (2012).CC BY · PubMed Central

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Authors: Gertig, U., & Hanisch, U.-K.
Affiliations: University of Göttingen (DE)
Corresponding author: Hanisch, Uwe-Karsten
Venue: Frontiers in Cellular Neuroscience
Publisher: Frontiers Media SA
Published: 2014-04-01
Volume: 8
Pages: 101-101
ISSN: 1662-5102 (ISSN-L)
DOI: 10.3389/fncel.2014.00101
PMC: PMC3978327
OpenAlex: W1968597551
Cited by: 123
References: 78
Citations by year: 2026: 2 · 2025: 2 · 2024: 4 · 2023: 5 · 2022: 10 · 2021: 9 · 2020: 11 · 2019: 12 · 2018: 6 · 2017: 18 · 2016: 13 · 2015: 23 · 2014: 8
FWCI: 1.67
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)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
GoeScholar The Publication Server of the Georg-August-Universität Göttingen (Georg-August-Universität Göttingen) (submittedVersion, cc-by)
Funders: Deutsche Forschungsgemeinschaft (SFB TRR 43, TRR-43)
Topics: Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
Keywords: microglia, microglial heterogeneity, microglial activation, inflammatory cytokines, debris removal, antigen presentation, neurotransmitter detection, CNS homeostasis, neuroinflammation, neuropathology

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