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 used the wild‐type Y strain (drug‐susceptible) of Trypanosoma cruzi and a drug‐resistant parasite population derived from the same strain. Trypomastigotes isolated from untreated infected mice, as well as, 3 h after treatment...

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Bibliographic Details
Published in:Parasite immunology 1999-10, Vol.21 (10), p.535-544
Main Authors: Murta, SMF, Ropert, C, Alves, RO, Gazzinelli, R T, Romanha, A J
Format: Article
Language:English
Subjects:
benznidazole
Chagas' disease
drug resistance
g-Interferon
interferon gamma
interleukin‐12
nitric oxide
reactive nitrogen intermediates
Trypanosoma cruzi
tumour necrosis factor alpha
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Summary:To study the effect of chemotherapy on parasite–macrophage interaction we used the wild‐type Y strain (drug‐susceptible) of Trypanosoma cruzi and a drug‐resistant parasite population derived from the same strain. Trypomastigotes isolated from untreated infected mice, as well as, 3 h after treatment with BZ were incubated with inflammatory macrophages and used to study phagocytosis, parasite destruction, cytokine release and reactive nitrogen intermediates (RNI) synthesis. Phagocytosis and destruction of the drug‐susceptible parasites were significantly enhanced by drug treatment. These enhancements were accompanied by an increase in cytokines [interleukin (IL)‐12 and tumour necrosis factor (TNF)α] and RNI release by murine inflammatory macrophages primed with IFN‐γ. In contrast, BZ treatment of mice infected with drug‐resistant T. cruzi population showed no effect whatsoever. The synthesis of IFN‐γ and RNI by splenocytes of mice infected with either susceptible and drug‐resistant parasite populations, before and after treatment with BZ were also studied. Only the splenocytes from mice infected with the drug‐susceptible parasites treated with BZ produced high levels of IFN‐γ and RNI. Our findings indicate that BZ acts on the drug‐susceptible T. cruzi parasites by enhancing the phagocytosis and the production of cytokines and RNI, thus, favouring the destruction of the intracellular parasites by the cellular compartment of the immune system.
ISSN:0141-9838
1365-3024
DOI:10.1046/j.1365-3024.1999.00251.x