Cytokine Production in Whole Blood Cultures from a Fishing Community in an Area of High Endemicity forSchistosoma mansoniin Uganda: the Differential Effect of Parasite Worm and Egg Antigens

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Abstract
The human host is continuously exposed to the egg and the adult worm developmental stages ofSchistosoma mansoniduring chronic infections with the parasite. To assess the cytokine responses induced by these different costimulating stages and how they are influenced by host age and infection intensity, whole blood samples from a cross-sectional cohort of 226 members of a Ugandan fishing community who had been resident in an area with high transmission ofS. mansonifor the previous 10 years or from birth were stimulated withS. mansoniegg antigen (SEA) or worm antigen (SWA). SWA-specific gamma interferon (IFN-γ) production increased with age, and the levels of SWA- and SEA-specific interleukin 3 (IL-3) were weakly correlated with schistosome infection intensity. The production of most cytokines was little affected by age or infection intensity but was either SEA or SWA specific. One hundred thirty-two members of the cohort coproduced IL-5 and IL-13 specifically in response to SWA, whereas only 15 produced these cytokines, and at much lower levels, in response to SEA. IL-10, IL-4, and IFN-γ were also produced in response to SWA, whereas the response to SEA consisted almost exclusively of IL-10. Our results suggest that, in contrast to what has been described for the murine model ofS. mansoniand during acute human infections, chronic intense exposure to and infection withS. mansoniin this cohort resulted in very low levels of response to SEA in vitro in the presence of a vigorous and mixed Th1-Th2 response to SWA.