Host microbiota constantly control maturation and function of microglia in the CNS.
- Erny D Institute of Neuropathology, University of Freiburg, Freiburg, Germany.
- Hrabě de Angelis AL Institute of Neuropathology, University of Freiburg, Freiburg, Germany.
- Jaitin D Lab for ImmunoGenomics, Weizmann Institute of Science, Rehovot, Israel.
- Wieghofer P 1] Institute of Neuropathology, University of Freiburg, Freiburg, Germany. [2] Faculty of Biology, University of Freiburg, Freiburg, Germany.
- Staszewski O Institute of Neuropathology, University of Freiburg, Freiburg, Germany.
- David E Lab for ImmunoGenomics, Weizmann Institute of Science, Rehovot, Israel.
- Keren-Shaul H Lab for ImmunoGenomics, Weizmann Institute of Science, Rehovot, Israel.
- Mahlakoiv T Department of Virology, University of Freiburg, Freiburg, Germany.
- Jakobshagen K Institute for Medical Microbiology, Immunology and Hygiene &Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.
- Buch T Institute for Medical Microbiology, Immunology, and Hygiene, Technische Universität München, Munich, Germany.
- Schwierzeck V Institute of Medical Microbiology and Hygiene, University of Mainz Medical Centre, Mainz, Germany.
- Utermöhlen O Institute for Medical Microbiology, Immunology and Hygiene &Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.
- Chun E Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts, USA.
- Garrett WS Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts, USA.
- McCoy KD Mucosal Immunology Lab, Department of Clinical Research, University of Bern, Bern, Switzerland.
- Diefenbach A Institute of Medical Microbiology and Hygiene, University of Mainz Medical Centre, Mainz, Germany.
- Staeheli P Department of Virology, University of Freiburg, Freiburg, Germany.
- Stecher B Max-von-Pettenkofer Institute, LMU Munich, German Center for Infection Research (DZIF), partner site LMU Munich, Munich, Germany.
- Amit I Lab for ImmunoGenomics, Weizmann Institute of Science, Rehovot, Israel.
- Prinz M 1] Institute of Neuropathology, University of Freiburg, Freiburg, Germany. [2] BIOSS Centre for Biological Signaling Studies, University of Freiburg, Freiburg, Germany.
- 2015-06-02
Published in:
- Nature neuroscience. - 2015
Animals
Central Nervous System
Fatty Acids, Volatile
Female
Homeostasis
Immunity, Innate
Male
Mice
Mice, Inbred C57BL
Microbiota
Microglia
Receptors, G-Protein-Coupled
English
As the tissue macrophages of the CNS, microglia are critically involved in diseases of the CNS. However, it remains unknown what controls their maturation and activation under homeostatic conditions. We observed substantial contributions of the host microbiota to microglia homeostasis, as germ-free (GF) mice displayed global defects in microglia with altered cell proportions and an immature phenotype, leading to impaired innate immune responses. Temporal eradication of host microbiota severely changed microglia properties. Limited microbiota complexity also resulted in defective microglia. In contrast, recolonization with a complex microbiota partially restored microglia features. We determined that short-chain fatty acids (SCFA), microbiota-derived bacterial fermentation products, regulated microglia homeostasis. Accordingly, mice deficient for the SCFA receptor FFAR2 mirrored microglia defects found under GF conditions. These findings suggest that host bacteria vitally regulate microglia maturation and function, whereas microglia impairment can be rectified to some extent by complex microbiota.
- Language
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- English
- Open access status
- green
- Identifiers
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- DOI 10.1038/nn.4030
- PMID 26030851
- Persistent URL
- https://sonar.ch/global/documents/169996
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