Recombinant Fasciola hepatica fatty acid binding protein (Fh15) reduces pro-inflammatory cytokines and modulates leukocyte infiltration in a DSS-induced ulcerative colitis mouse model 3681

Abstract Description Ulcerative colitis (UC), the most common inflammatory bowel disease in the U.S., affects approximately 286 people per 100,000 annually and is characterized by a pro-inflammatory immune response with colonic leukocyte infiltration, notably macrophages and neutrophils. The absence of a curative treatment for UC highlights the need for new therapies. Previous studies suggest that helminths, either by natural or artificial infections, might protect people from UC. We have demonstrated that a helminth-derived molecule (Fh15) reduces DSS-induced UC inflammation. We hypothesized that Fh15 may also modulate leukocyte infiltration in UC. To test this, C57BL/6 male mice were assigned to four groups (PBS, DSS, DSS-Fh15, Fh15). Colitis was induced in mice by providing ad-libitum drinking water with 4% DSS for 7 days. Fh15 was administered intraperitoneally at 2.0 mg/kg on days 1, 3, and 5. After confirming the development of UC in mice, we assessed macrophage and neutrophil populations. qPCR analysis showed that Fh15 reduced pro-inflammatory cytokines TNFα and IL-1β in the distal colon, both of which are secreted mainly by macrophages. Fh15 also decreased serum myeloperoxidase, which is mostly secreted by neutrophils. By immunohistochemistry, we quantified colonic areas stained for macrophages (F4/80) and neutrophils (Ly6G), finding that Fh15 significantly reduced leukocyte infiltration. In conclusion, Fh15 modulates immune cells, reducing colonic leukocyte infiltration and improving UC. Funding Sources Supported by NIAID grant SC1 AI159439 Topic Categories Mucosal and Regional Immunology (MUC)