Trypanosoma cruzi infects human dendritic cells and prevents their maturation: Inhibition of cytokines, HLA-DR, and costimulatory molecules

Trypanosoma cruzi, a parasitic protozoan, is the etiological agent of Chaga s' disease. Despite the many immune system disorders recognized in this inf ection and the crucial role played by dendritic cells (DC) in acquired immu ne responses, it was not known whether these cells could be infected by T. cruzi trypomastigotes and the consequences of such an infection on their im mune functions. We now provide evidence that human monocyte-derived DC can be infected by T. cruzi and can support its intracellular multiplication. I nterestingly, this infection has functional consequences on immature DC and on their maturation induced by lipopolysaccharide (LPS). First, after T. c ruzi infection, the basal synthesis of interleukin-12 (IL-12) and tumor nec rosis factor alpha (TNF-alpha) was impaired. Furthermore, the process of ma turation of DC induced by LPS was drastically affected by T. cruzi infectio n. Indeed, secretion of cytokines such as IL-12, TNF-alpha, and IL-6, which are released normally at high levels by LPS-activated DC, as well as the u p-regulation of HLA-DR and CD40 molecules, was significantly reduced after this infection. The same effects could be induced by T. cruzi-conditioned m edium, indicating that at least these inhibitory effects were mediated by s oluble factors released by T. cruzi. Taken together, these results provide new insights into a novel efficient mechanism, directly involving the alter ation of DC function, which might be used by T. cruzi to escape the host im mune responses in Chagas' disease and thus might favor persistent infection .