We compared the effects of larval and adult worm excretory-secretory (ES) products from hookworm on the proliferative responses and cytokine secretion in peripheral blood mononuclear cells (PBMCs) from hookwormpatients and egg-negative, nonendemic controls. When compared with negative controls, mitogen-stimulated PBMC from hookworm-infected individuals showed a significantly reduced proliferative response when adult worm ES antigen was added to the cultures. Furthermore, in hookworm-infected individuals a significant downmodulation of inflammatory interleukin (IL)-6 and tumor necrosis factor (TNF)- secretion resulted when PBMCs were stimulated with mitogen in combination with larval or adult worm ES. Both, interferon (IFN)- and IL-10 secretion were significantly lower in stimulated PBMC from infected individuals; however the IFN- /IL-10 ratio was much lower in hookworm-infected patients. Comparable effects, although at lower concentrations, were achieved when PBMCs from both groups were incubated with living hookworm third-stage larvae. We suggest that hookworm ES products downmodulate proliferative responses and inflammation during the chronic phase of the disease and facilitate early larval survival or adult worm persistence in the gut. 1. Introduction Helminth excretory-secretory products (ES) contain a vast mixture of antigens, are potent modulators of the host’s immune response, and therefore are important factors in worm survival and maintenance of a chronic human infection. ES products from different parasite species and different stages of parasitic development within the host were shown to downmodulate Type 1 immunity [1]. Among other mechanisms, early effects on dendritic cell function and innate immune responses have been previously described for intestinal nematode models [2], as well as for filarial infections [3, 4] with these events contributing to minimize inflammatory responses and induce a Type 2 response [1]. For hookworms, many components in ES products have been described so far [5, 6]; however, their effect on the human immune response is still not well understood and has become, more recently, a topic of intense investigation. We have recently reported that PBMCs from Necator americanus-infected patients had a lower production of TNF- and IL-10 in response to ES antigen derived from adult Ancylostoma caninum. Apart from the downmodulated cytokine secretion in response to ES antigen, PBMCs from endemic patients proliferated poorly in response to crude ES antigen extracts [7]. In the present study, we compare the effects of hookworm
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