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 Trypansoma cruzi population.
To stuck 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 (RN!) synthesis. Phagocytosis and destruction of the drug-susceptible parasites were significant/v enhanced by drug treatment. These enhancements were accompanied by an increase in cytokines [interleukin (IL)-12 and tumour necrosis factor (TNF)alpha] and RNI release by murine inflammatory macrophages primed with IFN-gamma. In contrast, BZ treatment of mice infected with drug-resistant T. cruzi population showed no effect whatsoever. The synthesis of IFN-gamma and RNI by splenocytes of mice infected with either susceptible and drug-resistant parasite populations, before and after treatment with BZ were also studied. On/v 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 cytokines and RN!, thus, favouring the destruction of the intracellular parasites by the cellular compartment of the immune system.
Murta
S M
SM
Departmento de Bioquímica e Immunologia, Brazil.
Ropert
C
C
Alves
R O
RO
Gazzinelli
R T
RT
Romanha
A J
AJ
D000818:Animals; D014355:Chagas Disease / Q000188:drug therapy* / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis*; D004351:Drug Resistance; D018664:Interleukin-12 / Q000096:biosynthesis; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis; D009593:Nitroimidazoles / Q000627:therapeutic use*; D018512:Parasitemia / Q000188:drug therapy*; D010587:Phagocytosis / Q000187:drug effects*; D014344:Trypanocidal Agents / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D016207:Cytokines; D009593:Nitroimidazoles; D014344:Trypanocidal Agents; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D009569:Nitric Oxide; C009999:benzonidazole