Trypanosoma cruzi promotes maturation of dendritic cells and the recruitment of proteins involved in antigen cross-presentation to the parasitophorous vacuole

BISCARI, LUCÍA; ALLOATTI, ANDRÉS

Congreso; Reunion Conjunta SAIC.SAI.AAFE.NANOMED; 2021

Sociedad Argentina de Inmunología

CD8 + T cells are key components of the immune response against Trypanosoma cruzi,and in this sense, the design of vaccines that induce such responses may be promising.In this work, a vaccination strategy based on mouse bone marrow-derived dendriticcells ?BMDCs?, incubated with a parasitic peptide TsKb20 ? derived from thetransialidase protein of T. cruzi ? and activated with LPS, was designed in order toinduce a TsKb20-specific CD8 + T cell response. The experimental scheme was asfollows: C57BL/6 mice were immunized intravenously with 50,000 TsKb20-loadedBMDCs, followed by a boost two weeks later. One group of animals was immunizedwith BMDCs not activated and not loaded with peptide (negative control). Fifteen daysafter the boost, cell suspensions derived from lymph nodes were cultured for 15 h with50 uM TsKb20. The specific CD8 + T cell response was measured by flow cytometryevaluating CD25 + and CD69 + activation markers in the CD8 + T cell population. Throughnon-parametric Mann-Whitney test, it was found that the TsKb20-specific CD8 + T cellresponse in animals immunized with peptide-loaded BMDCs was significantly higherthan in negative control animals. The same results were obtained by measuring IFN-γproduction by ELISPOT after restimulation with the peptide, or by staining withspecific tetramers. Another pool of animals was immunized and then challenged with2000 T. cruzi trypomastigotes. Female mice, but not male mice, showed lowerparasitemia and increased survival compared to negative control animals. These resultssuggest that the adoptive transfer of BMDCs could be used as a strategy to induce anti-T. cruzi CD8 + T cell responses, although these appear to be protective only in femalemice.