Dual role of monocyte-derived dendritic cells in Trypanosoma cruzi infection.

Pathogens can cause inflammation when inoculated into the skin. The vector-transmitted protozoan parasite Trypanosoma cruzi induces poor cellular-infiltration and disseminates, causing high mortality in the experimental model. Here, we characterized the inflammatory foci at the parasite inoculation site and secondary lymphoid organs using a murine model. While no macrophages and few neutrophils and monocytes (Mo) were recruited into the skin, T. cruzi infection elicited the mobilization of Ly6C(+) Mo to draining lymph nodes and spleen. Over time, this population became enriched in CD11b(+)Ly6C(+)CD11c(+)MHCII(+)CD86(+) cells resembling inflammatory dendritic cells (DCs). Adoptive transfer of Ly6C(+) Mo purified from the bone marrow of CD11c-GFP transgenic mice confirmed the monocytic origin of Ly6C(+) DCs found in the spleen of infected animals. Isolated Mo-derived cells not only produced TNF-alpha and nitric oxide, but also IL-10 and displayed a poor capacity to induce lymphoproliferation. Ablation of Mo-derived cells by 5-fluorouracil confirmed their dual role during infection, limiting the parasite load by inducible nitric oxide synthase-related mechanisms and negatively affecting the development of anti-parasite T-cell response. This study demonstrated that consistent with their antagonistic properties, these cells not only control the parasite spreading but also its persistence in the host.