The initiation and function of Th2 responses during infection with Schistosoma mansoni

Through experiments in which pro-inflammatory mediators have been neutralized in schistosomeinfected WT and IL-4 -/- mice we have been investigating the nature of the immune response that is required to allow survival during the period of acute disease that accompanies the onset of egg production by the parasitic worms. The developing picture is that of an early pro-inflammatory type-1 like response (characterized by the production of IFN-gamma and TNF-alpha and NO) which in the short term is able to control the deleterious effects on the liver associated with the arrival of the eggs, followed rapidly by a potent egg-induced Th2 response which simultaneously subsumes the role of protecting the liver and downregulates the production of the inflammatory mediators, thereby averting the serious consequence associated with the continued high level production of NO. Current research is directed towards: 1) understanding how pro-inflammatory mediators are protective during schistosomiasis, and 2) elucidating the underlying mechanisms through which the Th response is biased in a Th2 direction following exposure to schistosome eggs.