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

Abstract

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‐α 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.