title: Expression of the Blood-Group-Related Gene B4galnt2 Alters Susceptibility to Salmonella Infection.
abstract: 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.
authors.affiliation: Institute for Experimental Medicine, Christian-Albrechts-University of Kiel, Kiel, Germany; Max Planck Institute for Evolutionary Biology, Plön, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Rausch
authors.affiliation: Institute for Experimental Medicine, Christian-Albrechts-University of Kiel, Kiel, Germany; Models of Inflammation, Research Center Borstel, Borstel, Germany.
authors.forename: Natalie
authors.initials: N
authors.lastname: Steck
authors.affiliation: Institute for Experimental Medicine, Christian-Albrechts-University of Kiel, Kiel, Germany.
authors.forename: Abdulhadi
authors.initials: A
authors.lastname: Suwandi
authors.affiliation: Institute for Experimental Medicine, Christian-Albrechts-University of Kiel, Kiel, Germany.
authors.forename: Janice A
authors.initials: JA
authors.lastname: Seidel
authors.affiliation: Max Planck Institute for Evolutionary Biology, Plön, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Künzel
authors.affiliation: Department of Pediatrics, Division of Gastroenterology, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Kirandeep
authors.initials: K
authors.lastname: Bhullar
authors.affiliation: Institute for Laboratory Animal Science, Hannover Medical School, Hannover, Germany.
authors.forename: Marijana
authors.initials: M
authors.lastname: Basic
authors.affiliation: Institute for Laboratory Animal Science, Hannover Medical School, Hannover, Germany.
authors.forename: Andre
authors.initials: A
authors.lastname: Bleich
authors.affiliation: Research Institute, Puget Sound Blood Center, Seattle, Washington, United States of America; Department of Medicine, University of Washington, Seattle, Washington, United States of America.
authors.forename: Jill M
authors.initials: JM
authors.lastname: Johnsen
authors.affiliation: Department of Pediatrics, Division of Gastroenterology, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Vallance
authors.affiliation: Institute for Experimental Medicine, Christian-Albrechts-University of Kiel, Kiel, Germany; Max Planck Institute for Evolutionary Biology, Plön, Germany.
authors.forename: John F
authors.initials: JF
authors.lastname: Baines
authors.affiliation: Institute for Experimental Medicine, Christian-Albrechts-University of Kiel, Kiel, Germany; Models of Inflammation, Research Center Borstel, Borstel, Germany.
authors.forename: Guntram A
authors.initials: GA
authors.lastname: Grassl
mesh_terms: D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D000069196:Gastrointestinal Microbiome / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006790:Host-Parasite Interactions / Q000502:physiology; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007413:Intestinal Mucosa / Q000382:microbiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017350:N-Acetylgalactosaminyltransferases / Q000096:biosynthesis* / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012481:Salmonella Infections, Animal / Q000235:genetics* / Q000382:microbiology; D012486:Salmonella typhimurium; D014162:Transfection
chemical_list: D017350:N-Acetylgalactosaminyltransferases; C071413:beta-1,4-N-acetyl-galactosaminyl transferase 2