ANTIGEN PRESENTING CELLS AND IMMUNOMODULATION MEDIATED BY DIFFERENT INFECTIVE STAGES OF T. cruzi

BRENDA GUTIERREZ; SEBASTIÁN BIAGINI; ESTELA LAMEL; MARCEL RAMIREZ; STELLA M GONZALEZ CAPPA; CAROLINA PONCINI

Buenos Aires

Congreso; Reunión conjunta de sociedades de biociencias; 2017

ANTIGEN PRESENTING CELLS AND IMMUNOMODULATION MEDIATED BY DIFFERENTINFECTIVE STAGES OF T. cruziDendritic cells (DCs) are key players mediating the innate and the adaptiveimmune 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 the effect of bTp andmetacyclic (m)Tp from culture, in vitro in two different subsets of DCs, CD-MOand XS106, a cell line derived from epidemic DCs (Mohan, 2005). Furthermore,we studied the extent of these results in vivo in the experimental model ofinfection after T. cruzi intradermal inoculation.By flow cytometry, we better characterized the phenotype and functionalproperties 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 in CD-MO. Co-culture of XS106 or CD-MO 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 inthe recruitment of leukocytes into the site of infection. Animals inoculated with mTp displayed 100% of survival and no parasite detected in blood, while bTpinoculation induced 80% of mortality in addition to high parasitemia. Infectionwith mTp was confirmed by parasite detection at the site of infection in the skin and in the spleen by PCR. The challenge of mTp-infected animals byintraperitoneal infection with a lethal doses of bTp two weeks after the initialinoculation showed high activation of splenic DCs and control of the parasiteload in blood and tissues. These results suggest that mTp obtained in vitro fromepimastigotes and bTp triggered different early immune response.