Intact glycoconjugates from Taenia crassiceps excreted/secreted products ameliorate chemically induced colitis by modulating inflammation and strengthening adherens junctions

Background Ulcerative colitis (UC) is a chronic inflammatory disease that is increasing in prevalence worldwide. Notably, helminth infections, known for their immunoregulatory properties, are inversely related to inflammatory conditions such as UC. Research has indicated that Taenia crassiceps infection can improve inflammatory-mediated diseases, including type 1 diabetes, experimental autoimmune encephalomyelitis, and colitis. Subsequent studies revealed that helminth-derived products can replicate the effects of complete infection in the context of inflammatory diseases; however, the mechanisms underlying these effects remain unclear. This study examined the impact of intact glycans from T. crassiceps excreted/secreted products (TcES) on host responses to dextran sodium sulfate (DSS)-induced colitis. Methods UC was induced by administering 4% DSS in the drinking water for 9 days. The mice were treated with intact TcES, glycan-depleted TcES, or protein-depleted TcES 2 days after colitis induction. Symptoms of the disease, along with immunologic and histopathological evaluations, were performed. Results Colitic mice that received intact TcES presented fewer disease symptoms and less histopathological damage. Intact TcES reduced the proinflammatory response while increasing the production of IL-4, IL-22, IL-31, and MCP-1 and promoting M2 macrophage polarization via PD-L2 expression. Furthermore, intact TcES diminished neutrophil infiltration, inhibited NF-κB and p38 phosphorylation in the colon, and suppressed reactive oxygen species and 3-nitrotyrosine levels, thus protecting the colon. These effects were accompanied by increased expression of E-cadherin and β-catenin, indicating improved epithelial barrier integrity. Conversely, mice treated with glycan-depleted or protein-depleted TcES exhibited exacerbated colitis characterized by disruption of colon tissue architecture, extensive inflammation, and epithelial damage, including loss of E-cadherin and β-catenin and a lack of M2 macrophage polarization. ...