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ENTAMOEBA HISTOLYTICA INDUCES A ROBUST ACUTE INFLAMMATORY RESPONSE WITH INCREASED COLONIC PERMEABILITY AND ALTERED TIGHT JUNCTION PROTEINS IN MUC2-/- MICE
V Kissoon-Singh, F Moreau, K ChadeeGastrointestinal Research Group, University of Calgary, Calgary, AB
Aims: The intestinal MUC2 mucus layer is the first line of innate host defense against pathogens. Mice deficient in Muc2 spontaneously develop colitis and are more susceptible to DSS induced injury. The colonic parasite Entamoeba histolytica (Eh) exploits the mucus layer by binding of the parasite Gal/GalNAc lectin to mucin oligosaccharides to facilitate colonization leading to infectious disease in humans.
Methods: In this study we investigated the innate host defenses in Muc2-/- mice challenged with virulent Eh in a colonic loop model of infection.
Results: Eh induced a time dependent robust secretory response in Muc2-/- mice associated with increased pathology and leakage of serum albumin (p<0.01). The acute inflammation was dominated by elevated IFN-gamma and TNF-alpha protein secretion. Surprisingly, Eh caused an increased expression of the pore forming tight junction protein claudin-2 and a corresponding decreased expression of claudin-4 and occludin (p<0.05).
Conclusions: In the absence of Muc2, Eh elicits a robust acute inflammatory response and expression of TJ proteins leading to increased intestinal permeability emphasizing the role of Muc2 in luminal and epithelial barrier functions.