title: Priming of natural killer cells by nonmucosal mononuclear phagocytes requires instructive signals from commensal microbiota.
abstract: Mononuclear phagocytes are an important component of an innate immune system perceived as a system ready to react upon encounter of pathogens. Here, we show that in response to microbial stimulation, mononuclear phagocytes residing in nonmucosal lymphoid organs of germ-free mice failed to induce expression of a set of inflammatory response genes, including those encoding the various type I interferons (IFN-I). Consequently, NK cell priming and antiviral immunity were severely compromised. Whereas pattern recognition receptor signaling and nuclear translocation of the transcription factors NF-κB and IRF3 were normal in mononuclear phagocytes of germ-free mice, binding to their respective cytokine promoters was impaired, which correlated with the absence of activating histone marks. Our data reveal a previously unrecognized role for postnatally colonizing microbiota in the introduction of chromatin level changes in the mononuclear phagocyte system, thereby poising expression of central inflammatory genes to initiate a powerful systemic immune response during viral infection.
authors: IMMH, Institute of Medical Microbiology and Hygiene, University of Freiburg, Hermann-Herder-Strasse 11, Freiburg, Germany.
authors: Stephanie C
authors: SC
authors: Ganal
authors: Stephanie L
authors: SL
authors: Sanos
authors: Carsten
authors: C
authors: Kallfass
authors: Karin
authors: K
authors: Oberle
authors: Caroline
authors: C
authors: Johner
authors: Carsten
authors: C
authors: Kirschning
authors: Stefan
authors: S
authors: Lienenklaus
authors: Siegfried
authors: S
authors: Weiss
authors: Peter
authors: P
authors: Staeheli
authors: Peter
authors: P
authors: Aichele
authors: Andreas
authors: A
authors: Diefenbach
mesh_terms: D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D007370:Interferon Type I / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D054892:Metagenome / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010586:Phagocytes / Q000276:immunology* / Q000378:metabolism; D014777:Virus Diseases / Q000276:immunology
chemical_list: D016207:Cytokines; D007370:Interferon Type I