MHC Variation Sculpts Individualized Microbial Communities That Control Susceptibility to Enteric Infection

Details

• Alternative Title:
  Nat Commun
• Personal Author:
  Kubinak, Jason L. ; Stephens, W. Zac ; Soto, Ray ; Petersen, Charisse ; Chiaro, Tyson ; Gogokhia, Lasha ; Bell, Rickesha ; Ajami, Nadim J. ; Petrosino, Joseph F. ; Morrison, Linda ; Potts, Wayne K. ; Jensen, Peter E. ; O’Connell, Ryan M. ; Round, June L.
• Description:
  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.
• Subjects:
  Animals Article Disease Susceptibility Enteritis Female Gastrointestinal Microbiome Heterozygote Immunoglobulin A Intestinal Mucosa Lactobacillus Major Histocompatibility Complex Male Mice, Inbred BALB C Phenotype Polymorphism, Genetic Salmonella Enterica Salmonella Infections, Animal Symbiosis

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• Source:
  Nat Commun. 6:8642
• Pubmed ID:
  26494419
• Pubmed Central ID:
  PMC4621775
• Document Type:
  Journal Article
• Funding:
  DP2 AT008746/AT/NCCIH NIH HHSUnited States/ ; P40 OD010995/OD/NIH HHSUnited States/ ; K22 AI95375/AI/NIAID NIH HHSUnited States/ ; DP2 GM111099/GM/NIGMS NIH HHSUnited States/ ; N01AI95375/AI/NIAID NIH HHSUnited States/ ; R00 HL102228/HL/NHLBI NIH HHSUnited States/ ; P30 DK034987/DK/NIDDK NIH HHSUnited States/ ; DP2AT008746-01/AT/NCCIH NIH HHSUnited States/ ; T32 AI-055434/AI/NIAID NIH HHSUnited States/ ; 1S10RR026802-01/RR/NCRR NIH HHSUnited States/ ; S10 RR026802/RR/NCRR NIH HHSUnited States/ ; 5-P39-DK034987/DK/NIDDK NIH HHSUnited States/ ; T32 AI055434/AI/NIAID NIH HHSUnited States/ ; AI109122/AI/NIAID NIH HHSUnited States/ ; K22 AI095375/AI/NIAID NIH HHSUnited States/ ; DP2GM111099-01/DP/NCCDPHP CDC HHSUnited States/ ; R56 AI107090/AI/NIAID NIH HHSUnited States/ ; AI107090/AI/NIAID NIH HHSUnited States/ ; T32 GM007464/GM/NIGMS NIH HHSUnited States/ ; R21 AI109122/AI/NIAID NIH HHSUnited States/ ; 5-P40-OD010995/OD/NIH HHSUnited States/ ; R00HL102228-05/HL/NHLBI NIH HHSUnited States/
• Volume:
  6
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:40c1cc030e7c54767610cef502583f4fc16c0c4ebe30d1e274a73250ce2149e7
• Download URL:
  https://stacks.cdc.gov/view/cdc/37418/cdc_37418_DS1.pdf
• File Type:
  [PDF - 1.61 MB ]