Secretory IgA N-glycans contribute to the protection against E. coli O55 infection of germ-free piglets
Leona Rašková Kafková, Diana Brokešová, Michal Křupka, Zuzana Stehlíková, Jiří Dvořák, Štěpán Coufal, Alena Fajstová, Dagmar Šrůtková, Kateřina Štěpánová, Petra Hermanová, Renáta Štëpánková, Ivo Überall, Jozef Škarda, Zdeněk Novák, Luca Vannucci, Helena Tlaskalová‐Hogenová, Zuzana Jirásková Zákostelská, Marek Šinkora, Jiří Městecký, Milan Raška
Abstract
Mucosal surfaces are colonized by highly diverse commensal microbiota. Coating with secretory IgA (SIgA) promotes the survival of commensal bacteria while it inhibits the invasion by pathogens. Bacterial coating could be mediated by antigen-specific SIgA recognition, polyreactivity, and/or by the SIgA-associated glycans. In contrast to many in vitro studies, only a few reported the effect of SIgA glycans in vivo. Here, we used a germ-free antibody-free newborn piglets model to compare the protective effect of SIgA, SIgA with enzymatically removed N-glycans, Fab, and Fc containing the secretory component (Fc-SC) during oral necrotoxigenic E. coli O55 challenge. SIgA, Fab, and Fc-SC were protective, whereas removal of N-glycans from SIgA reduced SIgA-mediated protection as demonstrated by piglets' intestinal histology, clinical status, and survival. In vitro analyses indicated that deglycosylation of SIgA did not reduce agglutination of E. coli O55. These findings highlight the role of SIgA-associated N-glycans in protection. Further structural studies of SIgA-associated glycans would lead to the identification of those involved in the species-specific inhibition of attachment to corresponding epithelial cells.