Alteration of migration and maturation of dendritic cells and T-Cell depletion in the course of experimental Trypanosoma cruzi infection

Trypanosoma cruzi, the etiologic agent of Chagas disease, induces infection that affects most immunocompetent cells. However, its effect on dendritic cells (DC) is still unknown in vivo. In this report, we show, by immunohistochemical staining, that T. cruzi infection triggers a huge increase in the number of CD11c(+) DC in the spleen of infected mice at Days 14 and 21 post-inoculation (pi). In mice reaching the chronic phase (starting on Day 35 pi), the number of splenic DC (sDC) returned progressively to normal (ending on Day 98 pi). In the spleens of noninfected mice, most of the CD8alpha(+)CD11c(+) and CD8alpha(-)CD11c(+) DC were found in the red pulp and the marginal and T-cell zones. However, starting on Day 14 pi, a progressive decline of CD8alpha(+)CD11c(+) was observed. In addition, sDC expressed low levels of the costimulatory molecule B7.2 at Days 14 and 21 pi, suggesting that they remained immature in the course of the infection. As expected, in lipopolysaccharide-treated and noninfected mice, the expression of B7.2 molecules was sharply up-regulated on sDC that migrated toward the T-cell zone. In contrast, upon lipopolysaccharide stimulation, sDC from T. cruzi-infected mice did not migrate toward the T-cell zone nor did they undergo maturation. Finally, white pulp was severely depleted in both CD4(+) and CD8(+) T cells at the peak of infection. Taken together, these results indicate that profound alterations of migration and maturation of sDC and depletion/redistribution of T cells occur during the acute phase of T. cruzi infection and could be part of another strategy to escape immune surveillance and to persist in the host.