Toxicity of Paraquat in Isolated Rat Lung. Search for Efficient Antidotes

Abstract

The immune evasion mechanisms of pathogenic trypanosomatids involve a multitude of phenomena such as the polyclonal activation of lymphocytes, cytokine modulation and the enhanced detoxification of oxygen reactive species. A trypanothione-cascade seems to be involved in the detoxification process. We have recently described and characterized a tryparedoxin (LiTXN1) involved in the Leishmania infantum cytoplasmatic hydroperoxide metabolism. LiTXN1 is a secreted protein upregulated in the infectious form of the parasite, suggesting that it can play an important role during infection. In the present study, we investigated whether the recombinant LiTXN1 (rLiTXN1) would affect T and B cell functions in a murine model. We observed a significant increase of CD69 surface marker on the B-cell population in total spleen and on isolated B-cells from BALB/c mice after in vitro rLiTXN1 stimulus. Activated Bcells underwent further proliferation, as measured by an increased [3H]-thymidine incorporation. Cytokine quantification showed a dose-dependent upregulation of IL-10 secretion. B-cells were identified as a source. Furthermore, intraperitoneal injection of rLiTXN1 into BALB/c mice triggered the production of elevated levels of rLiTXN1 specific antibodies, predominantly of the IgM, IgG1 and IgG3 isotypes, with a minimum reactivity against other heterologous antigens. Taken together, our data suggest that rLiTXN1 could participate in the immunopathological processes by targeting the B-cells effector functions with subsequent IL-10 secretion and specific antibodies production.