Trypanosoma cruzi upregulates nitric oxide release by IFN-gamma-preactivated macrophages, limiting cell infection independently of the respiratory burst.
The relationship between nitric oxide (N = O) produced by mouse peritoneal macrophages (MPM) and Trypanosoma cruzi infection is still poorly understood. The conditions of MPM activation by gamma-interferon (IFN-gamma) to trigger a N = O-dependent trypanocidal activity, as well as the effect of parasite infection or of reactive oxygen species (ROS) inhibitors on the N = O release were studied. T. cruzi infection occurring after a previous 24 h MPM activation induced an enhancement of nitrite levels (the stable degradation product of N = O) in cell supernatants; both the percentage of infected MPM and the number of amastigotes per infected cell were decreased in comparison to infected but non-activated MPM. Addition of superoxide dismutase or catalase to non-infected but activated MPM increased the nitrite levels; these were not detectable when L-arginine inhibitors were added together with ROS inhibitors. The latter had no effect on infection nor on nitrite levels when infection occurred after pre-activation, and induced only a weak nitrite release when infection took place before MPM activation. Altogether, these results support the involvement of N = O in the inhibition of T. cruzi infection by IFN-gamma-preactivated macrophages, together with the upregulation of N = O release by T. cruzi infection independently of the respiratory burst.
Metz
G
G
Laboratoire de Parasitologie Expérimentale, Faculté des Sciences, ULB, Brussels.
Carlier
Y
Y
Vray
B
B
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002374:Catalase / Q000494:pharmacology; D002478:Cells, Cultured; D007371:Interferon-gamma / Q000494:pharmacology*; D008262:Macrophage Activation; D017737:Macrophages, Peritoneal / Q000378:metabolism / Q000469:parasitology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000096:biosynthesis*; D011994:Recombinant Proteins; D016897:Respiratory Burst; D013482:Superoxide Dismutase / Q000494:pharmacology; D014349:Trypanosoma cruzi / Q000378:metabolism*; D015854:Up-Regulation; D019323:omega-N-Methylarginine
D011994:Recombinant Proteins; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D007371:Interferon-gamma; D001120:Arginine; D002374:Catalase; D013482:Superoxide Dismutase