TRYPANOSOMA-CRUZI UP-REGULATES 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 peritone al macrophages (MPM) and Trypanosoma cruzi infection is still poorly u nderstood The conditions of MPM activation by gamma-interferon (IFN-ga mma) to trigger a N=O-dependent trypanocidal activity, as well as the effect of parasite infection or of reactive oxygen species (ROS) inhib itors on the N=O release were studied. T. cruzi infection occurring af ter a previous 24 h MPM activation induced an enhancement of nitrite l evels (the stable degradation product of N=O) in cell supernatants bot h the percentage of infected MPM and the number of amastigotes per inf ected 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 nor delectable when L-arginine inhibitors were added together with ROS inhibitors. Th e latter had no effect on infection nor on nitrite levels when infecti on occured after pre-activation, and induced only a weak nitrite relea se when infection took place before MPM activation. Altogether, these results support the involvement of N=O in the inhibition of T. cruzi i nfection by IFN-gamma-preactivated macrophages, together with the upre gulation of N=O release by T. cruzi infection independently of the res piratory burst.