Pathogenic mechanisms in Blastocystis spp. - Interpreting results from in vitro and in vivo studies.

Blastocystis spp. are commonly reported intestinal protists but whose clinical significance remains controversial. Infections have ranged from asymptomatic carriage to non-specific gastrointestinal symptoms and have also been linked to irritable bowel syndrome and urticaria in some patient populations. In vitro studies showed that both parasite and parasite lysates have damaging effects on intestinal epithelial cells causing apoptosis and degradation of tight junction proteins occludin and ZO1, resulting in increased intestinal permeability. Adhesion of trophic forms to the intestinal epithelium and release of cysteine proteases appear to be the major triggers leading to pathogenesis. Two putative virulence factors identified are cysteine proteases legumain and cathepsin B. Blastocystis spp. also have immuno-modulatory effects including degradation of IgA, inhibition of iNOS and upregulation of proinflammatory cytokines, IL8 and GM-CSF in intestinal epithelial cells and IL1β, IL6 and TNFα in murine macrophages. Blastocystis spp. have also been reported to dampen response to LPS in intestinal epithelial cells and monocytes. Studies in rodent models and naturally infected pigs have shown that the parasite localizes to the lumen and mucosal surface of the large intestine mostly in the caecum and colon. The parasite has been found to cause mucosal sloughing, increase in goblet cell mucin, increased intestinal permeability and to induce a pro-inflammatory cytokine response with upregulation of TNFα, IFNγ and IL12. In this review, we summarize findings from in vitro and in vivo studies that demonstrate pathogenic potential but also show considerable inter and intra subtype variation, which provides a plausible explanation on the conflicting reports on clinical significance.