In-vivo treatment with benznidazole enhances phagocytosis, parasite destruction and cytokine release by macrophages during infection with a drug-susceptible but not with a derived drug-resistant Trypanosoma cruzi population

To study the effect of chemotherapy on parasite-macrophage interaction we u sed the wild-type Y strain (drug-susceptible) of Trypanosoma cruzi and a dr ug-resistant parasite population derived from the same strain. Trypomastigo tes isolated from untreated infected mice, as well as, 3 h after treatment with BZ were incubated with inflammatory macrophages and used to study phag ocytosis, parasite destruction cytokine release and reactive nitrogen inter mediates (RNI) synthesis. Phagocytosis and destruction of the drug-suscepti ble parasites were significantly enhanced by drug treatment. These enhancem ents were accompanied by an increase in cytokines [interleukin (IL)-12 and tumor necrosis factor (TNF)alpha] and RNI release by murine inflammatory ma crophages primed with IFN-gamma. In contrast, BZ treatment of mice infected with drug-resistant T. cruzi population showed no effect whatsoever. The s ynthesis of IFN-gamma and RNI by splenocytes of mice infected with either s usceptible and drug-resistant parasite populations, before and after treatm ent with BZ were also studied. Only the splenocytes from mice infected with the drug-susceptible parasites treated with BZ produced high levels of IFN -gamma and RNI. Our findings indicate that BZ acts on the drug-susceptible T. cruzi parasites by enhancing the phagocytosis and the production of cyto kines and RNI, thus, favouring the destruction of the intracellular parasit es by the cellular compartment of the immune system.