| The host-parasite relationship is a complex one that often results from centuries of co-evolution. Schistosomiasis is one such disease that has infected humans for millennia, as eggs of the species Schistosoma haematobium have been found in the kidneys of twentieth-dynasty Egyptian mummies. Schistosomiasis continues to be a major human health problem in many developing countries. The major Schistosoma species that infect humans are S. mansoni, S. haematobium, and S. japonicum . Approximately 200 million people are afflicted with the disease, with 800,000 people die per year of complications associated with schistosomiasis. Ironically, economic progress has increased the prevalence of schistosomiasis over the last 30 years, because the snail hosts thrive in the still, fresh waters of irrigation canals and reservoirs. Therefore, the search for effective prophylaxis is an area of much current research. For this to be accomplished, the mechanisms involved in the pathogenesis of schistosomiasis must first be unraveled.;Since the granuloma is the major pathologic manifestation of schistosomiasis, much research is devoted to understanding the factors contributing to the developing immune response to egg antigens and granuloma formation. The granuloma is a CD4+ T cell-dependent delayed type hypersensitivity (DTH) response Mediated primarily by the Th2 cytokine IL-4 and IL-13. The cytokine macrophage migration inhibitory factor (MIF) was postulated to participate in schistosome granuloma formation based on its contribution to the induction of the DTH response to mycobacterium. We therefore examined the effects of MIF neutralization on the development of the immune response to schistosome eggs. In vivo administration of a neutralizing antibody against MIF had no effect on Th2 cytokine production or cellular proliferation.;We next examined the effect of in vivo CD40 activation on the cytokine response to schistosome antigens. An agonistic alphaCD40 mAb blocked Th2 cytokines from egg-injected mice in an IFNgamma- and IL-12-dependent manner. Additionally, alphaCD40 induced IFNgamma production in an IL-12-independent manner. However, schistosome-infected mice treated with alphaCD40 displayed immunological and pathological measurements comparable to control mice, suggesting that in vivo CD40 activation is more effective at attenuating acute Th2-mediated responses than chronic infection. |
