Prophylactic Potential of Recombinant Taenia solium Calreticulin in Mice with TNBS-induced Colitis

Inflammatory bowel diseases (IBD) have been rising in developed countries. Multiple studies have shown that gastrointestinal helminths induce a regulatory environment, thus have been used to control IBD. Nonetheless treatment with living parasites is disadvantageous; therefore identification of parasitic immunomodulatory proteins is compulsory. Calreticulin is a calcium binding protein with key functions in the cell. Our group identified, cloned and generated Taenia solium calreticulin as a recombinant protein (rTsCRT). It induces a predominant Th2 response after oral immunization. Therefore, we investigated the prophylactic potential of rTsCRT in an experimental model of colitis. Mice were immunized with purified rTsCRT weekly for four weeks and colitis was induced by intra-rectal administration of trinitrobenzene sulfonic acid (TNBS). Three days later clinical disease activity, colonic inflammation, as well as cytokine production were assessed. Mice that did not receive TNBS showed no signs of disease or inflammation, which were increased in mice with colitis. rTsCRT immunization significantly decreased the clinical score index, the extent of colonic inflammation and the expression of IL-1, IL-6 and TNF. Colons of immunized mice overexpressed IL-13 and peritoneal macrophages from rTsCRT-treated mice produced more IL-10 as compared to cells from mice with colitis. rTsCRT also decreased MHCII expression in LPS-treated dendritic cells and induced expression of TGF-b. Additionally, we showed that rTsCRT reduces the genotoxicity produced by TNBS. We conclude that oral immunization with rTsCRT ameliorates TNBS-induced colitis in mice, suggesting that rTsCRT has immunomodulatory properties and prophylactic potential for the treatment of IBD.

Financial support: PAPIIT IN48132, UNAM, Mexico