Expression of the Blood-Group-Related Gene Alters Susceptibility to Infection

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Human blood groups are among the oldest known genetic polymorphisms. It has been proposed that blood group variation is a byproduct of pathogen-driven selection, including in the gastrointestinal tract where blood-group-related genes are often variably expressed. The B4galnt2 gene is responsible for the synthesis of the Sd(a)/Cad carbohydrate blood group antigen and displays variable tissue-specific expression patterns in wild mouse populations. Using an established model for Salmonella Typhimurium induced colitis, we found that loss of B4galnt2 expression in the intestinal epithelium decreases susceptibility to infection. These effects were strongly associated with the influence of B4galnt2 expression on the intestinal microbiota, whereby microbial diversity prior to infection was highly predictive of reduced inflammation and resistance to Salmonella Typhimurium infection. Additionally, B4galnt2 expression in blood vessels also distinctly influenced intestinal phenotypes and Salmonella susceptibility. These data lend new insights into bacterial community diversity as an “extended phenotype” that can be mediated by host genetic variation at blood-group-related genes. This work further provides strong experimental evidence in support of a scenario of complex selection on the B4galnt2 tissue-specific expression variants via host-microbe relationships and susceptibility to infectious disease.

Vyšlo v časopise: Expression of the Blood-Group-Related Gene Alters Susceptibility to Infection. PLoS Pathog 11(7): e32767. doi:10.1371/journal.ppat.1005008
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1005008

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