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MHC Variation Sculpts Individualized Microbial Communities That Control Susceptibility to Enteric Infection
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    The presentation of protein antigens on the cell surface by major histocompatibility complex (MHC) molecules coordinates vertebrate adaptive immune responses, thereby mediating susceptibility to a variety of autoimmune and infectious diseases. The composition of symbiotic microbial communities (the microbiota) is influenced by host immunity and can have a profound impact on host physiology. Here we use an MHC congenic mouse model to test the hypothesis that genetic variation at MHC genes among individuals mediates susceptibility to disease by controlling microbiota composition. We find that MHC genotype significantly influences antibody responses against commensals in the gut, and that these responses are correlated with the establishment of unique microbial communities. Transplantation experiments in germfree mice indicate that MHC-mediated differences in microbiota composition are sufficient to explain susceptibility to enteric infection. Our findings indicate that MHC polymorphisms contribute to defining an individual's unique microbial fingerprint that influences health.

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    1S10RR026802-01/RR/NCRR NIH HHS/United States
    5-P39-DK034987/DK/NIDDK NIH HHS/United States
    5-P40-OD010995/OD/NIH HHS/United States
    AI107090/AI/NIAID NIH HHS/United States
    AI109122/AI/NIAID NIH HHS/United States
    DP2AT008746-01/AT/NCCIH NIH HHS/United States
    DP2GM111099-01/DP/NCCDPHP CDC HHS/United States
    K22 AI095375/AI/NIAID NIH HHS/United States
    K22 AI95375/AI/NIAID NIH HHS/United States
    P40 OD010995/OD/NIH HHS/United States
    R00HL102228-05/HL/NHLBI NIH HHS/United States
    R21 AI109122/AI/NIAID NIH HHS/United States
    T32 AI-055434/AI/NIAID NIH HHS/United States
    T32 GM007464/GM/NIGMS NIH HHS/United States
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