Papel do adaptador indutor de Interferon-β contendo domínio TIR (TRIF) na resistência de camundongos a infecção por Neospora caninum

Abstract

Neospora caninum is an intracellular parasite that has the dog as its definitive host and other mammals, especially cattle, as intermediate hosts. Economically, neosporosis is an important disease in Veterinary medicine due to the induction of relevant clinical signs, as abortions in cattle and neuromuscular paralysis in dogs. The aim of this study was to evaluate the role of the TLR adaptor protein TRIF in the resistance against N. caninum infection. For this, in vitro experiments with bone marrow derived macrophages (BMDMs) from C57BL/6 wild-type (WT) and TRIF knockout (TRIF-/-) mice, stimulated by tachyzoites and in vivo infections, were performed in order to investigate the production of cytokines and antibodies, cellular and tissue parasitism, histological changes during different phases of infection and survival analysis. We observed that TRIF-/- BMDMs presented notable defects in inflammatory cytokine production in relation to WT macrophages. Additionally, we found that the concentration of NO, IL-12p40, IFN-y and TNF were decreased in peritoneal fluids and lungs of TRIF-/- mice, while IL-2, IFN-γ, TNF and IL-17 were reduced in sera of these animals compared to WT mice. Higher parasite burden was observed in peritoneal cells, lungs and brain during the acute and chronic phases of infection, which were associated with inflammatory changes in the analyzed tissues, while TRIF-/- mice survival rate decreased 2-fold compared to WT. In conclusion, our results show that TRIF is required for resistance against the infection induced by N. caninum, regulating the production of key Th1 cytokines and participating in the control of the tissue parasitism and inflammatory lesions induced against the parasite.