MHC variation sculpts individualized microbial communities that control susceptibility to enteric infection.
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.
Department of Pathology, Division of Microbiology and Immunology, University of Utah School of Medicine, Salt Lake City, Utah 84112, USA.
Jason L
JL
Kubinak
Department of Pathology, Division of Microbiology and Immunology, University of Utah School of Medicine, Salt Lake City, Utah 84112, USA.
W Zac
WZ
Stephens
Department of Pathology, Division of Microbiology and Immunology, University of Utah School of Medicine, Salt Lake City, Utah 84112, USA.
Ray
R
Soto
Department of Pathology, Division of Microbiology and Immunology, University of Utah School of Medicine, Salt Lake City, Utah 84112, USA.
Charisse
C
Petersen
Department of Pathology, Division of Microbiology and Immunology, University of Utah School of Medicine, Salt Lake City, Utah 84112, USA.
Tyson
T
Chiaro
Department of Pathology, Division of Microbiology and Immunology, University of Utah School of Medicine, Salt Lake City, Utah 84112, USA.
Lasha
L
Gogokhia
Department of Pathology, Division of Microbiology and Immunology, University of Utah School of Medicine, Salt Lake City, Utah 84112, USA.
Rickesha
R
Bell
Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas 77030, USA.|Department of Molecular Virology and Microbiology, Alkek Center for Metagenomics and Microbiome Research, Baylor College of Medicine, Houston, Texas 77030, USA.
Nadim J
NJ
Ajami
Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas 77030, USA.|Department of Molecular Virology and Microbiology, Alkek Center for Metagenomics and Microbiome Research, Baylor College of Medicine, Houston, Texas 77030, USA.
Joseph F
JF
Petrosino
Department of Biology, University of Utah, Salt Lake City, Utah 84112, USA.
Linda
L
Morrison
Department of Biology, University of Utah, Salt Lake City, Utah 84112, USA.
Wayne K
WK
Potts
Department of Pathology, Division of Microbiology and Immunology, University of Utah School of Medicine, Salt Lake City, Utah 84112, USA.
Peter E
PE
Jensen
Department of Pathology, Division of Microbiology and Immunology, University of Utah School of Medicine, Salt Lake City, Utah 84112, USA.
Ryan M
RM
O'Connell
Department of Pathology, Division of Microbiology and Immunology, University of Utah School of Medicine, Salt Lake City, Utah 84112, USA.
June L
JL
Round
D000818:Animals; D004198:Disease Susceptibility; D004751:Enteritis / Q000276:immunology*; D005260:Female; D000069196:Gastrointestinal Microbiome; D006579:Heterozygote; D007070:Immunoglobulin A / Q000235:genetics; D007413:Intestinal Mucosa / Q000276:immunology*; D007778:Lactobacillus; D008285:Major Histocompatibility Complex; D008297:Male; D008807:Mice, Inbred BALB C; D010641:Phenotype; D011110:Polymorphism, Genetic; D012481:Salmonella Infections, Animal / Q000276:immunology*; D019779:Salmonella enterica; D013559:Symbiosis
D007070:Immunoglobulin A