Avaliação da causa mortis em camundongos C57BL/6 infectados experimentalmente com Neospora caninum

Abstract

Neospora caninum is an obligate intracellular parasite that causes neuromuscular disease in dogs and abortion in cattle. It is distributed worldwide, leading to significant economic losses to cattle raisers. Experimental models in mice have been used to further understand the pathogenesis of this disease, although the cause of death in these animals is still unknown. In the present work we aimed to evaluate the cause of death in mice experimentally infected with N. caninum. All experiments were done using C57BL/6 female mice, infected with a lethal dose (3x107

) of tachyzoites of the N. caninum Liverpool (Nc-Liv) isolate. First, we observed through histopathological evaluation that the pancreas of the infected mice presented severe microscopic alterations. Based on experiments of the infected mice in a kinects of day, we found that lesions in the pancreas were already evident at day one after infection, confirming the acute characteristic of the pancreatitis. To understand the mechanism behind the cause of death, we aimed to determine whether the cytokines IL-12 and IFNγ play a role in acute pancreatitis. Initially, IL-12 production was observed, followed by an increase in IFNγ production five days post-infection. Furthermore, Il12-/-,

and Ifng -/-

, mice did not develop the pancreatic lesions found in WT mice, highlighting the role of both cytokines in the pathogenesis.We also determined that this phenomenon was only present after parenteral infections, since the lesions could only be observed in mice that received an intraperitoneal inoculation, and not on those that received parasite by gavage (oral) In conclusion, we have determined that lethal N. caninum infections in the mouse model are induced by an acute pancreatitis, that depends on the parenteral route of infection and IL-12 and IFNγ pathway.