Entamoeba histolytica Induces Paracellular Secretory Responses In Muc2 −/− Mice

MUC2 mucin (murine Muc2) produced by goblet cells forms the mucus layer as the first line of host defence against enteric pathogens. E. histolytica ( Eh ) binds Gal/GalNAc residues of MUC2 and prevents Eh from damaging the underlying epithelia. As Eh do not invade the mouse colon, we tested the host responses towards Eh in the colon of wild type (Wt) and Muc2 −/− mice (no mucus barrier) challenged with 10 6 virulent Eh trophozoites in colonic loop studies. In Muc2 −/− colons, Eh evoked a robust time‐dependent (1–6h) secretory response concomitant with increased leakage of serum albumin, IgA and IgG as compared to Wt controls. In Wt mice, there was a significant increase in the secretion of high molecular weight mucin, non‐mucus glycoproteins and IgA. Moreover, although Eh induced robust pro‐inflammatory and protein expression (TNF‐α, IFN‐γ, COX‐2) in Wt animals, the responses in Muc2 −/− mice was dampened. Neither Wt nor Muc2 −/− animals showed increased gene expression of the goblet cell mediators TFF‐3 or RELM‐β. These data demonstrate that Muc2 mucin plays a critical role in protection against paracellular secretory responses toward Eh in the gut. Curiously, undefined compensatory mechanisms in Muc2 −/− mice abrogated an excessive intestinal pro‐inflammatory response. This work was funded by CIHR.