Changes in Epithelial Barrier Function in Response to Parasitic Infection: Implications for IBD Pathogenesis

Background and Aims: Mast cells (MCs) are implicated in epithelial barrier alterations that characterize inflammatory and functional bowel disorders. In this study, we describe mast cell proteinases (chymases and tryptases) and tight junction (TJ) proteins kinetics in a rat model of postinfectious gut dysfunction. Methods: Jejunal tissues of control and Trichinella spiralis -infected rats were used. Inflammation-related changes in MCs and the expression of TJ-related proteins were evaluated by immunostaining and RT-qPCR. Epithelial barrier function was assessed in vitro (Ussing chambers) and in vivo . Results: After infection, intestinal inflammation was associated with a generalized overexpression of MC chymases, peaking between days 6 and 14. Thereafter, a mucosal MC hyperplasia and a late increase in connective tissue MC counts were observed. From day 2 post-infection, TJ proteins occludin and claudin-3 expression was down-regulated while the pore-forming protein claudin-2 was overexpressed. The expression of proglucagon, precursor of the barrier-enhancing factor glucagon-like peptide-2, was reduced. These changes were associated with an increase in epithelial permeability, both in vitro and in vivo . Conclusions: Proteinases expression and location of mucosal and connective tissue MCs indicate a time-related pattern in the maturation of intestinal MCs following T. spiralis infection. Altered expression of TJ-related proteins is consistent with a loss of epithelial tightness, and provides a molecular mechanism for the enhanced epithelial permeability observed in inflammatory conditions of the gut.