Cysteine protease-dependent mucus disruptions and differential mucin gene expression in Giardia duodenalis infection.

This study reveals a complex interaction at the surface of epithelial cells, between G. duodenalis and the intestinal mucus layer. Here, we reveal mechanisms whereby G. duodenalis evades and disrupts the first line of host defense by degrading human mucin-2 (MUC2), depleting mucin stores and inducing differential gene expression in the mouse small and large intestines. Human colonic biopsies exposed to G. duodenalis were depleted of mucus and in vivo, mice infected with G. duodenalis had a thinner mucus layer and demonstrated differential Muc2 and Muc5ac mucin gene expression. Infection in Muc2(-/-) mice elevated trophozoite colonization in the small intestine and impaired weight gain. In vitro, human LS174T goblet-like cells were depleted of mucus and had elevated levels of MUC2 mRNA expression following G. duodenalis exposure. Importantly, the cysteine protease inhibitor E64 prevented mucus degradation, mucin depletion, and the increase in MUC2 expression. This study demonstrates a novel role for Giardia's cysteine proteases in pathogenesis, and describes how Giardia's disruptions of the mucus barrier facilitate bacterial translocation that may contribute to the onset and propagation of disease. PMID: 28823873 [PubMed - as supplied by publisher]
Source: The American Journal of Pathology - Category: Pathology Authors: Tags: Am J Pathol Source Type: research