Professional Antigen Presenting Cells immunomodulation mediated by different infective stages of T. cruzi

BRENDA CELESTE GUTIÉRREZ; MARCEL RAMIREZ; SEBASTIAN BIAGINI; CAROLINA V. PONCINI; ESTELA LAMMEL

Congreso; REUNIÓN CONJUNTA DE SOCIEDADES DE BIOCIENCIAS; 2017

Dendritic cells (DCs) are key players mediating the innate and the adaptive immune response. Previously, we have reported that blood (b) trypomastigotes (Tp), negatively regulate the activity and function of bone-marrow derived DCs (CD-MO) in vitro. In the present work, we compared and analysed the effect of bTp and metacyclic (m)Tp from culture in vitro in two different subsets of DCs, CD-MO and XS106, a cell line derived from epidemic DCs. Furthermore, we studied the extent of these results in vivo in the experimental model of infection after T. cruzi intradermal inoculation. By flow cytometry, we better characterized the phenotype and functional properties of the XS106 cell line. We found F4/80, Ly6C, CD207, CD11b, CD11c, MHCII, CD40 and CD86 surface expression, confirming the myeloid origin of these cells in addition to a basal activation state, not affected by Tp (bTp or mTp). Moreover, by ELISA we detected TNF-α, and IL-10 downregulation in the presence of LPS+Tp, contrary to previous results reported for CD-MO. Cell infection in culture with bTp or mTp demonstrate that bTp presented enhanced infectivity in XS106 compared to mTp and to CD-MO. The experimental model of infection with bTp and mTp showed differences in the recruitment of leukocytes into the site of infection. Animals inoculated with mTp displayed 100% of survival and no parasite detected in blood, while bTp inoculation induced 80% of mortality in addition to high parasitemia. Infection with mTp was confirmed by PCR in the skin at the site of infection and spleen. The challenge of mTp-infected animals by intraperitoneal infection with bTp two weeks after the initial inoculation showed enhanced activation of splenic DCs and better control of the parasite load in tissues. These results suggest that mTp obtained in vitro from epimastigotes and bTp triggered different early immune response.