The innate immune response is critical in shaping the subsequent acquired immune response. As individuals living in endemic areas are liable to be exposed to infectious cercariae on multiple occasions during domestic, recreational, or occupational water contacts, it has been suggested that repeated exposure to E/S antigens Epigenetic Reader Domain inhibitor released by invading cercariae may modulate the host’s immune response . Indeed, in an experimental murine model, multiple infection
with S. mansoni cercariae down-modulated CD4+ T-cell responses in the skin-draining lymph nodes . Multiple infection also down-regulated the development of egg-specific responses in distant lymphoid tissues and modulated the size buy GDC-0068 of egg-induced granulomas in the liver . Therefore, human immune responsiveness to larval E/S material warrants investigation. Unfortunately, human immune responses to cercarial antigens have been infrequently investigated and have been restricted to preparations comprising the soluble fraction of whole cercariae (termed CAP or SCAP) [11-15]. This preparation is dominated by cytosolic components
recovered from the disrupted cercarial bodies and is therefore not reflective of larval E/S material. Analysis of human immune responses specifically to cercarial E/S material is unprecedented. The study presented here undertook to make an initial analysis of innate/early immune responsiveness to cercarial E/S (i.e. 0–3 h RP) in a cohort of patients from an area endemic
for schistosomiasis in northern Senegal. Specifically, the early cytokine response at 24 h of whole-blood (WB) cultures stimulated with 0–3 h RP was examined. The cytokines studied (i.e. IL-8, TNFα and IL-10) were chosen as ones typically released by innate immune cells such as macrophages and monocytes upon activation. Cytokine responses were compared Phosphatidylethanolamine N-methyltransferase between individuals who did not harbour patent schistosome infection, those infected with S. mansoni alone, and those co-infected with S. mansoni and S. haematobium to investigate whether responsiveness to larval E/S products is influenced by current infection status. We report that cercarial E/S antigens stimulated the release of greater quantities of regulatory IL-10, but not pro-inflammatory TNFα or IL-8, in participants infected with schistosomes compared with uninfected controls. This study was conducted in 2009 as part of a larger investigation (SCHISTOINIR) examining immune responses in three endemic countries , for which approval was obtained by the review board of the Institute of Tropical Medicine in Antwerp, the ethical committee of the Antwerp University Hospital and ‘Le Comité National d’Ethique de la Recherche en Santé’ in Dakar, Senegal. Informed and written consent were obtained from all participants; for children, informed consent was obtained from their parents or legal guardant.