Premium
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
Author(s) -
Silvane Maria Fonseca Murta,
Catherine Ropert,
Rosana Alves,
Ricardo T. Gazzinelli,
Álvaro J. Romanha
Publication year - 1999
Publication title -
parasite immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.795
H-Index - 75
eISSN - 1365-3024
pISSN - 0141-9838
DOI - 10.1046/j.1365-3024.1999.00251.x
Subject(s) - benznidazole , trypanosoma cruzi , phagocytosis , biology , population , macrophage , immune system , cytokine , microbiology and biotechnology , splenocyte , immunology , parasite load , interleukin 10 , in vivo , parasite hosting , in vitro , medicine , biochemistry , environmental health , world wide web , computer science
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 .