Metabolic regulation of cytokine production in leishmania resistance and susceptibility

Abstract

Abstract Leishmania, a protozoan parasite, ensures its survival inside its mammalian host by modulating host metabolism and immune response. Recent advances in the field of immune-metabolism have shown that the metabolic enzymes and metabolites have immune-modulatory functions. Leishmania infection of a susceptible host skews immune response towards Th2-type, enhances production of pro-parasitic cytokines IL-10 and IL-4 but reduces IFN-gamma and IL-12 production. By contrast, Leishmania infection of a resistant host sets an immune response bias towards Th1-type, results in high production of pro-inflammatory IL-12 and IFN-gamma, which activates macrophages to kill the intracellular amastigotes. To understand the role of metabolic factors in Leishmania susceptibility or resistance, we used L. donovani susceptible or resistant mouse strains BALB/c or 129/Sv, respectively. The mice were first intravenously infected with L. donovani, followed by intra-peritoneal treatment with different inhibitors of metabolic pathways. The splenocytes from the treated resistant and susceptible mouse strains were studied for in-situ cytokine response and T cell subsets by FACS. Also the mouse serum was used for cytokine estimation by ELISA. The results show that different metabolic pathways regulate cytokine production in L. donovani-infected mouse suggesting their role in resistance and susceptibility to Leishmania infection.