title: Host microbiota constantly control maturation and function of microglia in the CNS.
abstract: 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.
authors.affiliation: Institute of Neuropathology, University of Freiburg, Freiburg, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Erny
authors.affiliation: Institute of Neuropathology, University of Freiburg, Freiburg, Germany.
authors.forename: Anna Lena
authors.initials: AL
authors.lastname: Hrabě de Angelis
authors.affiliation: Lab for ImmunoGenomics, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Diego
authors.initials: D
authors.lastname: Jaitin
authors.affiliation: 1] Institute of Neuropathology, University of Freiburg, Freiburg, Germany. [2] Faculty of Biology, University of Freiburg, Freiburg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Wieghofer
authors.affiliation: Institute of Neuropathology, University of Freiburg, Freiburg, Germany.
authors.forename: Ori
authors.initials: O
authors.lastname: Staszewski
authors.affiliation: Lab for ImmunoGenomics, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Eyal
authors.initials: E
authors.lastname: David
authors.affiliation: Lab for ImmunoGenomics, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Hadas
authors.initials: H
authors.lastname: Keren-Shaul
authors.affiliation: Department of Virology, University of Freiburg, Freiburg, Germany.
authors.forename: Tanel
authors.identifier: 0000000190590486
authors.initials: T
authors.lastname: Mahlakoiv
authors.affiliation: Institute for Medical Microbiology, Immunology and Hygiene &Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.
authors.forename: Kristin
authors.initials: K
authors.lastname: Jakobshagen
authors.affiliation: Institute for Medical Microbiology, Immunology, and Hygiene, Technische Universität München, Munich, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Buch
authors.affiliation: Institute of Medical Microbiology and Hygiene, University of Mainz Medical Centre, Mainz, Germany.
authors.forename: Vera
authors.initials: V
authors.lastname: Schwierzeck
authors.affiliation: Institute for Medical Microbiology, Immunology and Hygiene &Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.
authors.forename: Olaf
authors.initials: O
authors.lastname: Utermöhlen
authors.affiliation: Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts, USA.
authors.forename: Eunyoung
authors.initials: E
authors.lastname: Chun
authors.affiliation: Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts, USA.
authors.forename: Wendy S
authors.initials: WS
authors.lastname: Garrett
authors.affiliation: Mucosal Immunology Lab, Department of Clinical Research, University of Bern, Bern, Switzerland.
authors.forename: Kathy D
authors.initials: KD
authors.lastname: McCoy
authors.affiliation: Institute of Medical Microbiology and Hygiene, University of Mainz Medical Centre, Mainz, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Diefenbach
authors.affiliation: Department of Virology, University of Freiburg, Freiburg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Staeheli
authors.affiliation: Max-von-Pettenkofer Institute, LMU Munich, German Center for Infection Research (DZIF), partner site LMU Munich, Munich, Germany.
authors.forename: Bärbel
authors.initials: B
authors.lastname: Stecher
authors.affiliation: Lab for ImmunoGenomics, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Ido
authors.initials: I
authors.lastname: Amit
authors.affiliation: 1] Institute of Neuropathology, University of Freiburg, Freiburg, Germany. [2] BIOSS Centre for Biological Signaling Studies, University of Freiburg, Freiburg, Germany.
authors.forename: Marco
authors.initials: M
authors.lastname: Prinz
mesh_terms: D000818:Animals; D002490:Central Nervous System / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D005232:Fatty Acids, Volatile / Q000276:immunology / Q000378:metabolism*; D005260:Female; D006706:Homeostasis / Q000276:immunology / Q000502:physiology*; D007113:Immunity, Innate / Q000276:immunology / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D064307:Microbiota / Q000276:immunology / Q000502:physiology*; D017628:Microglia / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled / Q000172:deficiency
chemical_list: D005232:Fatty Acids, Volatile; C506481:Ffar2 protein, mouse; D043562:Receptors, G-Protein-Coupled