[PDF][PDF] Priming of natural killer cells by nonmucosal mononuclear phagocytes requires instructive signals from commensal microbiota

SC Ganal, SL Sanos, C Kallfass, K Oberle, C Johner… - Immunity, 2012 - cell.com
SC Ganal, SL Sanos, C Kallfass, K Oberle, C Johner, C Kirschning, S Lienenklaus, S Weiss…
Immunity, 2012cell.com
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 …
Summary
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.
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