Dados do Trabalho

Título

Synergic effect of IL-4 and IFN-γ cytokine stimulus directing the L-arginine fate during Leishmania infantum infection

Introdução

Macrophages in Leishmania infection are a crucial mediator of immune response determining the infection outcome. We have shown that insulin-like growth factor I (IGF-I) expression are modulated by IL-4, IL-13, and IFN-γ cytokines in macrophages infected by Leishmania major. Extrinsic IL-4 and IGF-I are both involved in Leishmania intracellular proliferation acting on the L-arginine metabolic pathway.

Objetivo(s)

Here we studied the L-arginine metabolism during infection of L. infantum, aetiological agent of potentially lethal visceral leishmaniosis.

Material e Métodos

THP-1 macrophages obtained with PMA treatment in RPMI 1640 medium with 2% FBS, at 37˚C and 5% CO2 were infected with L. infantum stationary phase promastigotes (8/1). In some experiments, IL-4 and/or IFN-γ stimulus were used. Parasitism was evaluated by light microscopy, expression of Igf-I, Arg1, Nos2 and Leish-Arg mRNA by qPCR, arginase activity by Urea production and Nitric oxide by Griess reaction.

Resultados e Conclusão

The IL-4 and/or IFN-γ stimulus increase the Arg1, Nos2 and Igf-I mRNA expression. These stimuli have not a strong effect over the parasitism with slight increase upon IL-4, slight decrease upon IFN-γ and slight increase upon concomitant stimulus. Arginase activity increased upon IL-4, decrease upon IFN-γ and increase upon concomitant stimulus. The production of Nitric oxide increase upon concomitant stimulus. The Leishmania arginase mRNA expression decreased under IL-4 and/or IFN-γ stimulus.
During active visceral leishmaniosis IL-4 and IFN-γ are present in high concentrations. Our findings showing IL-4 and IFN-γ with marginal effect on parasitism reinforce the vain role of these cytokines. Our results suggest that concomitant stimulus increase the expression of main genes involved in L-arginine metabolism and polyamine production enhancer the human macrophage infection.

Palavras-chave

Leishmania infantum, L-arginine, macrophages, IGF-I