MHC variation sculpts individualized microbial communities that control susceptibility to enteric infection

TLDR

MHC molecules coordinate adaptive immune responses, influencing susceptibility to autoimmune and infectious diseases, while host immunity shapes microbiota composition, which in turn impacts host physiology. The study tests whether MHC genetic variation among individuals modulates disease susceptibility by shaping gut microbiota composition using a congenic mouse model. An MHC congenic mouse model was used to assess how MHC genotype affects gut microbiota and antibody responses. MHC genotype drives distinct antibody responses to commensals and establishes unique gut microbial communities, and transplantation of these microbiota into germfree mice demonstrates that such differences confer differential susceptibility to enteric infection, underscoring MHC polymorphisms as determinants of individual microbial fingerprints that influence health.

Abstract

Abstract 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.