B cell-deficient mice infected with Trypanosoma cruzi develop a pro-inflammatory T cell response potentially harmful for the host.

GOROSITO SERRAN, MELISA; TOSELLO BOARI, JIMENA; BERMEJO, DANIELA A; FIOCCA VERNENGO, FACUNDO; MONTES CAROLINA L; ACOSTA RODRIGUEZ E V; GRUPPI ADRIANA

Puerto Varas

Jornada; XXVII Annual Meeting, Chilean Society For Cell Biology. Octubre de 2013; 2013

B cell-deficient mice (C129.BL6mMT) infected with T. cruzi, have more parasitemia than C57BL/6 wild type (WT) mice and accelerated mortality. To assess possible causes of this increased susceptibility, we analyzed the production of cytokines and the CD4+T-cell response in infected mMT and WT mice. Mice were infected by i.p. injection of 10000 trypomastigotes Y-br strain. Groups of 4-7 mice were sacrificed on days 4, 9, 15, 20 post-infection (pi); splenocytes were obtained and CD4+ T cells were studied by flow-cytometry. In addition, serum samples were obtained to quantify IFNg and TNF by ELISA. Both infected mice strains presented by day 9 (pi) increased amounts of serum IFNg, being higher in mMT mice (p<0.01). Serum TNF amounts were increased in both mice strains by day 9pi but afterward diminished in WT mice and increased in mMT mice (days 16 and 20pi, p<0.001). When we studied the dis-regulated IFNg and TNF-producing cells, we observed that the CD4+ population, the main IFNg producer by day 9pi, was increased in mMT mice (p=0.0013). The CD4+ population was the main TNF producer by days 15 and 20pi. Serum cytokines kinetics correlated with the splenic CD4+ T cell population. In addition, mMT mice showed a diminished percentage of IL10-producing CD4+ T cells on day 9pi (p=0.0013), but no significant changes in serum IL10. Furthermore, we determined that mMT CD4+ lymphocytes have a diminished CTLA-4 and PD1 expression (p<0.01) and increased Fas expression (p<0.05). Finally, we observed that mMT infected mice had a lower percentage of effector (CD44+CD62L-) and an augmented percentage of naive (CD62L+CD44-) CD4+ T cells (days 9 and 15pi p<0.01). Conclusion: Our data suggests that B-cell absence during T. cruzi infection could cause an altered activation of the CD4+ population, which presents a naive phenotype and is capable of producing inflammatory cytokines, leading to a systemic imbalance in the host.