The acute phase of Chagas' disease in mice and human is marked by states of immunosuppression, in which Trypanosoma cruzi replicates extensively and releases immunomodulatory molecules that delay parasite-specific responses mediated by effector T cells. This mechanism of evasion allows the parasite to spread in the host. Parasite molecules that regulate the host immune response during Chagas’ disease have not been fully identified, particularly proteins of the amastigote stage. In this work, we evaluated the role of the GPI anchored SSP4 protein of T. cruzi as an immunomodulatory molecule in peripheral blood mononuclear cells (PBMCs). rMBP::SSP4 protein was able to stimulate nitric oxide (NO) production. Likewise, rMBP::SSP4 induced the expression of genes and production of molecules involved in the inflammatory process, such as, cytokines, chemokines, and adhesion molecules (CAMs) as determined by RT-PCR and ELISA. These results suggest that the amastigote SSP4 molecule could play a key role in the immunoregulatory and/or immunosuppressive process observed in the acute phase of infection with T. cruzi. 1. Introduction Chagas’ disease is a zoonosis caused by the protozoan parasite Trypanosoma cruzi, and it is a major public health problem in most of Latin America and in particular in Mexico. Indeed, the WHO estimates that about 8–11 million persons are infected worldwide [1]. T. cruzi infects many cell types, including myocytes, fibroblast, vascular endothelial, and smooth muscle cells among other cells. Since the monocyte is a target cell in T. cruzi infection and monocytes play a major role in regulating immune responses, monocyte dysfunction may contribute to host immunosuppression [2]. It has been observed that during the experimental infection with T. cruzi, there is an increased expression of proinflammatory mediators, including cytokines [3], chemokines [4], vascular adhesion molecules [5], and nitric oxide synthase [6] among other molecules [7], which promotes the inflammatory process and vascular damage. There is evidence that immune mechanisms are involved in the pathogenesis of many parasitic infections. The initial stages of the disease are generally characterized by the induction of a nonspecific lymphoproliferation, which is believed to disrupt antigen recognition and interfere with protective immune responses. Paradoxically, in most cases, a state of immunosuppression can be evidenced. This hyporesponsiveness to antigen-specific and polyclonal stimuli in chronic parasitic infections could be related to immunosuppressive cytokines secreted
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