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

PLoS Pathogens

Guntram A. Grassl¹  Andre Bleich²  Kirandeep Bhullar³  Philipp Rausch³  Abdulhadi Suwandi³  Sven Künzel³  Jill M. Johnsen⁴  Bruce A. Vallance⁴  Marijana Basic⁵  Natalie Steck⁵  Janice A. Seidel⁶  John F. Baines⁷ 

[1] Department of Medicine, University of Washington, Seattle, Washington, United States of America;Department of Pediatrics, Division of Gastroenterology, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada;Institute for Experimental Medicine, Christian-Albrechts-University of Kiel, Kiel, Germany;Institute for Laboratory Animal Science, Hannover Medical School, Hannover, Germany;Max Planck Institute for Evolutionary Biology, Plön, Germany;Models of Inflammation, Research Center Borstel, Borstel, Germany;Research Institute, Puget Sound Blood Center, Seattle, Washington, United States of America

关键词: Salmonella typhimurium;    Gastrointestinal tract;    Inflammation;    Salmonellosis;    Species diversity;    Salmonella;    Mouse models;    Microbiome;   

DOI  :  10.1371/journal.ppat.1005008

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Glycans play important roles in host-microbe interactions. Tissue-specific expression patterns of the blood group glycosyltransferase β-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.

【 授权许可】

CC BY