Cruzipain, the major cystein protease of T. cruzi, inhibits the maturation of antigen presenting cells.

DELETTIERES D; VERMEULEN M; FRANK FM; CAZORLA SI; GEFFNER J; MALCHIODI EL

Córdoba

Congreso; VIIº Congreso Latinoamericano de Inmunología; 2005

Acute phase of Chagas disease is associated with a severe unresponsiveness to antigens and mitogens. We have previously reported that cruzipain (Cz), the major cystein protease of T. cruzi, administered with ODN CpG generates protective immune response against a lethal challenge. Dendritic cells (DC) are the most potent antigen presenting cells and play an essential role in T-cell priming during in vivo infection. We analyzed the effect of Cz on DC, obtained from bone marrow progenitors of C57BL/6 mice cultured with GM-CSF for 9 days. We evaluated the phenotype and the uptake of OVA-FITC by flow citometry in DC pulsed with Cz at 37oC and compared with non-stimulated ones (Ct). Cz reduced the endocytosis of OVA-FITC (Cz 28±6; Ct 46±9) and expression of MHC-II (Cz 267±23; Ct 356±33), whereas the expression of CD11b was improved (Cz 64±6; Ct 22±2) (mean fluorescence intensity ± SE, n=3, p<0,05). Secretion of IL10 and TNFa in the supernatant of DC were analyzed, by ELISA, founding a 3.4 and 11.6 fold increase over Ct respectively. Then, we examined the ability of DC to stimulate allogeneic T cell from splenocytes of BALB/C mice. A 2.7 fold decrease in MLR was observed in DC pulsed with Cz, effect that was reverted by stimulation of CpG, founding a 4 fold increase in proliferation.             Taken together, these results suggest that Cz could be responsible for the immunosupression observed in the acute phase of Chagas disease and this could be prevented by the immunomodulation effects of CpG.