Cathepsin L of Fasciola hepatica meliorates colitis by altering the gut microbiome and inflammatory macrophages

Helminths can relieve the development of autoimmune diseases and inflammatory diseases, by inducing anti-inflammatory innate immune responses. Here, we report that CL7, a Cathepsin L protein secreted by Fasciola hepatica, inhibited the activation of the NF-κB and MAPK signaling resulting in reduced secretion of inflammatory mediators in macrophages. Furthermore，we found that CL7 could prevent dextran sulfate sodium (DSS) induced ulcerative colitis (UC). CL7 and ESP administration restored DSS-induced body weight loss, colon shortening, and injury, significantly decreased the disease activity index (DAI) and alleviated colonic epithelial injury. CL7 noticeably suppressed the DSS-triggered M1 polarization upregulation and inhibited IL-17 and other inflammatory mediator production in UC mice. Additionally, CL7 ameliorated DSS-induced microbiota dysbiosis. Results of Antibiotic treatment (ABX) and fecal microbial transplants (FMT) suggested that the gut microbiota played an important role in CL7 treating UC. These findings propose that CL7 could be a promising strategy for UC therapy.