Cryptosporidium parvum disrupts intestinal epithelial barrier function via altering expression of key tight junction and adherens junction proteins

Abstract Infection with the protozoan parasite Cryptosporidium parvum (CP) causes cryptosporidiosis, a widespread diarrheal disease. Impaired intestinal epithelial barrier function and increased permeability are most commonly associated with diarrheal diseases caused by enteric infections. However, studies on barrier disruption and underlying mechanisms in cryptosporidiosis are extremely limited. Epithelial tight junctions (TJ) and adherens junctions (AJ) are important in maintaining barrier integrity. Therefore, we examined the effects of CP infection on paracellular permeability and on the expression of the major TJ and AJ proteins utilizing in vitro, ex vivo, and in vivo models. CP infection (0.5 x 106 oocysts/well in Transwell inserts, 24 h) increased paracellular permeability (FITC‐dextran flux) in Caco‐2 cell monolayers and substantially decreased the protein levels of occludin, claudin 4 and E‐cadherin. Claudin 3, zonula occludens‐1 (ZO1) and α‐catenin were also significantly decreased, whereas claudin 1 and 2 and β‐catenin were not altered. Substantial downregulation of occludin, claudin 4 and E‐cadherin was also observed in response to CP infection ex vivo in mouse enteroid‐derived monolayers, and in vivo in the ileal and jejunal mocosa of C57BL/6 mice. The mRNA levels of these proteins were also significantly decreased in CP infected mouse ileum and jejunum, but were unaltered in Caco‐2 cells. Further, bafilomycin, an inhibitor of lysosomal proto...
Source: Cellular Microbiology - Category: Microbiology Authors: Tags: RESEARCH ARTICLE Source Type: research