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Expression of the Blood-Group-Related Gene B4galnt2 Alters Susceptibility to Salmonella Infection
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نویسنده
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rausch p. ,steck n. ,suwandi a. ,seidel j.a. ,künzel s. ,bhullar k. ,basic m. ,bleich a. ,johnsen j.m. ,vallance b.a. ,baines j.f. ,grassl g.a.
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منبع
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plos pathogens - 2015 - دوره : 11 - شماره : 7
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چکیده
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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. © 2015 rausch et al.
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آدرس
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institute for experimental medicine,christian-albrechts-university of kiel,kiel,germany,max planck institute for evolutionary biology,plön, Germany, institute for experimental medicine,christian-albrechts-university of kiel,kiel,germany,models of inflammation,research center borstel,borstel, Germany, institute for experimental medicine,christian-albrechts-university of kiel,kiel, Germany, institute for experimental medicine,christian-albrechts-university of kiel,kiel, Germany, max planck institute for evolutionary biology,plön, Germany, department of pediatrics,division of gastroenterology,child and family research institute,university of british columbia,vancouver,bc, Canada, institute for laboratory animal science,hannover medical school,hannover, Germany, institute for laboratory animal science,hannover medical school,hannover, Germany, research institute,puget sound blood center,seattle,wa,united states,department of medicine,university of washington,seattle,wa, United States, department of pediatrics,division of gastroenterology,child and family research institute,university of british columbia,vancouver,bc, Canada, institute for experimental medicine,christian-albrechts-university of kiel,kiel,germany,max planck institute for evolutionary biology,plön, Germany, institute for experimental medicine,christian-albrechts-university of kiel,kiel,germany,models of inflammation,research center borstel,borstel,germany,institute of medical microbiology and hospital epidemiology,hannover medical school,hannover,germany,german center for infection research (dzif),hannover, Germany
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Authors
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