Proteína de Grânulo Denso 48 (GRA48) de Neospora caninum Atua na Fase Crônica da Neosporose Experimental

Abstract

Neospora caninum is a protozoan parasite that causes abortion in cattle worldwide. These abortions result in significant economic losses for the livestock industry. N. caninum invasion of host cells are followed by the formation of a parasitophorous vacuole (PV). Some N. caninum dense granular proteins (NcGRAs) are essential for PV formation, which is essential for the virulence of the parasite. In this context, the main objective of this study was to determine the role of N. caninum dense granule protein 48 (GRA48) in virulence and regulation of the host immune response. C57BL/6 mice were intraperitoneally infected with N. caninum tachyzoites from the NcLiv (WT), NcLiv∆gra48 or non-infected (NI) to evaluate body weight and, additionally, parasitic load during chronic and acute phase. The cytokine profile of IFN-γ and IL-12p40 was evaluated by ELISA during the acute infection in the spleen, peritoneal lavage, and serum of infected and NI mice. In addition, IL-10 and IL-12p40 from supernatant of the culture of bone marrow-derived macrophages (BMDMs) infected with NcLiv (WT), NcLiv∆gra48 or NI were analyzed. Mice infected with the NcLiv∆gra48 showed less weight loss and brain parasitism during chronic phase of the infection, however, there were no differences in the acute phase. Pro-inflammatory cytokines, such as IFN-γ and IL-12p40, did not show significant differences between the WT and NcLiv∆gra48 during the acute phase in the spleen and serum. In macrophages, the absence of GRA48 resulted in a significantly decreased IL-12p40 and IL-10, indicating its role in modulating the immune response. Thus, the results demonstrated that N. caninum GRA48 may play role in the parasite biology and immune response.