B4galnt2-mediated host glycosylation influences the susceptibility to infection.

Histo-blood group antigens in the intestinal mucosa play important roles in host-microbe interactions and modulate the susceptibility to enteric pathogens. The gene, expressed in the GI tract of most mammals, including humans, encodes a beta-1,4-N-acetylgalactosaminyltransferase enzyme which catalyzes the last step in the biosynthesis of the Sd(a) and Cad blood group antigens by adding an N-acetylgalactosamine (GalNAc) residue to the precursor molecules. In our study, we found that loss of expression is associated with increased susceptibility to infection, a murine model pathogen for human enteropathogenic We observed increased histopathological changes upon infection in mice lacking B4galnt2 compared to -expressing wild-type mice. In addition, wild-type mice cleared the infection faster than knockout mice. It is known that uses its type 1 fimbriae adhesive subunit to bind specifically to D-mannose residues on mucosal cells. Flow cytometry analysis of intestinal epithelial cells showed the absence of GalNAc-modified glycans but an increase in mannosylated glycans in deficient mice compared to sufficient mice. Adhesion assays using intestinal epithelial organoid-derived monolayers revealed higher adherence to cells lacking expression compared to wild-type cells which in turn was reduced in the absence of type I fimbriae. In summary, we show that expression modulates the susceptibility to infection, which is partly mediated by fimbriae-mannose interaction.