Papel da enzima oxido nítrico sintase induzível na infecção por Neospora caninum

Abstract

Neospora caninum is an Apicomplexan parasite, closely related to Toxoplasma gondii. Since its first description, N. caninum infection has emerged as an important cause of economic loss in the cattle industry. Inducible nitric oxide synthases (iNOS) is the most important enzyme responsible for the generation of Nitric Oxide (NO), which is classically described as an important effector mechanism in the killing of intracellular pathogens. For that purpose, we aimed to evaluate the role of inducible nitric oxide synthases during N. caninum infection. The results obtained here suggest the involvement of iNOS in modulation of the cytokine profile produced by macrophages, once targeted genetic disruption of this enzyme led to a decrease in the inflammatory cytokines production (IL-12p40, TNF- and IL-1) and an increase in IL-10 levels in macrophages infected with N. caninum. Our results obtained from experimentally infected mice indicate that iNOS is an important resistance mechanism in the N. caninum infection, by inducing the control of acute and chronic parasitism, cytokine production and consequently the exacerbation of the inflammatory responses. After infecting with N. caninum, wild type C57BL/6 mice (WT) had a lower mortality rate, parasitism and inflammation if compared to iNOS-/- mice, besides having lower early Th1 cytokine profile levels and Th2/Th17 in an intermediate stages of infection. Based on these results, we conclude that iNOS is important in modulating immune responses during N. caninum infection, by controlling parasitism, thereby inhibiting cytokine overproduction and consequently the deleterious effects of immunopathological processes.