Fas-FasL interaction modulates nitric oxide production in Trypanosoma cruzi-infected mice

During acute Trypanosoma cruzi infection in mice, many leucocytes undergo a poptosis. Although apoptosis has been ascribed to increased levels of nitri c oxide (NO) and Fas-FasL interaction, the importance of this phenomenon in modulating the host response against T. cruzi is unknown. Herein, the role of NO- and Fas-FasL-induced apoptosis in modulating the immune response to T. cruzi was evaluated using mice deficient in Fas expression (MRL/MpJ-Fas lpr) and inducible nitric oxide synthase (iNOS) knockout mice (iNOS-/-). T he results showed that besides decreasing apoptosis induction after infecti on, impairment of the Fas-FasL interaction resulted in decreased NO product ion, as a consequence of enhanced T helper 2 (Th2) cytokine production. Dif ferently, blockage of NO-induced apoptosis resulted in uncontrolled cytokin e production, rather than a biased Th2 cytokine pattern. Together, these re sults suggested that Fas and Fast-induced apoptosis could be implied in mod ulation of the immune response against T. cruzi by interfering with cytokin e and NO production during the acute phase of the infection.