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Publication : Expression of the Blood-Group-Related Gene B4galnt2 Alters Susceptibility to Salmonella Infection.

First Author  Rausch P Year  2015
Journal  PLoS Pathog Volume  11
Issue  7 Pages  e1005008
PubMed ID  26133982 Mgi Jnum  J:247297
Mgi Id  MGI:5918578 Doi  10.1371/journal.ppat.1005008
Citation  Rausch P, et al. (2015) Expression of the Blood-Group-Related Gene B4galnt2 Alters Susceptibility to Salmonella Infection. PLoS Pathog 11(7):e1005008
abstractText  Glycans play important roles in host-microbe interactions. Tissue-specific expression patterns of the blood group glycosyltransferase beta-1,4-N-acetylgalactosaminyltransferase 2 (B4galnt2) are variable in wild mouse populations, and loss of B4galnt2 expression is associated with altered intestinal microbiota. We hypothesized that variation in B4galnt2 expression alters susceptibility to intestinal pathogens. To test this, we challenged mice genetically engineered to express different B4galnt2 tissue-specific patterns with a Salmonella Typhimurium infection model. We found B4galnt2 intestinal expression was strongly associated with bacterial community composition and increased Salmonella susceptibility as evidenced by increased intestinal inflammatory cytokines and infiltrating immune cells. Fecal transfer experiments demonstrated a crucial role of the B4galnt2-dependent microbiota in conferring susceptibility to intestinal inflammation, while epithelial B4galnt2 expression facilitated epithelial invasion of S. Typhimurium. These data support a critical role for B4galnt2 in gastrointestinal infections. We speculate that B4galnt2-specific differences in host susceptibility to intestinal pathogens underlie the strong signatures of balancing selection observed at the B4galnt2 locus in wild mouse populations.
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