Dual role of monocyte-derived inflammatory cells in T. cruzi infection

STELLA M GONZÁLEZ CAPPA; CAROLINA V. PONCINI

Mar del Plata

Encuentro; LXIV Reunión Anual de la Sociedad Argentina de Inmunología. Reunión conjunta SAIC-SAI-SAFE; 2016

Pathogens can cause inflammation when inoculated into the skin. The vector-transmitted protozoan parasite Trypanosoma cruzi induces poor cell-infiltration at the beginning of the infection and disseminates causing high mortality in experimental models.Here, we characterized the inflammatory foci at the parasite inoculation siteand secondary lymphoid organs. While no macrophages, neutrophils or monocytes(Mo) recruited into the skin at 3 days post-infection, a population of Ly6CMo infiltrated first draining lymph nodes and then the spleen. Over time, theinfiltrate became enriched in CD11b CD11c Ly6C cells, resembling inflammatory dendritic cells (iDCs) previously reported in other infections. Adoptive transfer of Mo purified from bone marrow of CD11cGFP transgenic mice confirmed that iDC-like cells found in the spleen of infected mice were from monocytic origin. Freshly isolated iDC-like cells not only produced TNF and nitric oxide, but also IL-10 and displayed impaired capacity to induce lymphoproliferation. Toexplore their myeloid-suppressor nature, infected mice were treated with5-fluorouracil. The treatment reduced CD11b CD11c Ly6C cell number and confirmed its dual role, firstly by controlling parasite dissemination by iNOS-related mechanisms and then by the negative regulation of T cell-dependent anti-parasite response.