Immune Modulations of a Helminth Derived Protein

Abstract

The immune responses at the gastrointestinal mucosa modulate nematode parasite infection, initially characterized by the production of epithelium-derived, robust T helper 2 (Th2) type alarmin cytokines, such as interleukin (IL)-25, IL-33, and thymic stromal lymphopoietin (TSLP). Subsequently, the immune responses are mediated by releasing the lymphoid cell-derived Th2 immune cytokines, such as IL-13, IL-4, IL-5, IL-9, and parasite-specific antibodies. Studies have shown that parasitic nematode worms can establish a chronic infection in the intestine, even in a robust immune response. This evidence leads us to hypothesize that the nematode evolves to evade or regulate intestinal immunity through specific modulatory mechanisms that interfere with initial intestinal immune responses, allowing the nematode to survive. We used a model nematode, Heligmosomoides polygyrus bakeri (Hpb), to identify nematode-derived proteins with regulatory effects on Th2 immune cytokines during chronic infection. Through high throughput analysis, we found that a Hpb-derived protein could precisely modulate mouse immune response. The presence of the Hpb-derived protein was essential for the parasite's survival as the vaccine conferred a sterilizing immunity. As Th2 cytokines are directly associated with the pathogenesis of several inflammatory and autoimmune diseases, we are understanding how this protein regulates the function of the Th2 cytokines in vitro and in vivo and explore whether the protein could use to treat inflammatory diseases and serve as a vaccine target to control nematode infections.