Inflammasome activation restrains the intracellular Neospora caninum proliferation in bovine macrophages

Abstract

Neospora caninum is an intracellular parasite that causes neosporosis in cattle. Bovine neosporosis is considered a major cause of bovine abortion worldwide. Rapid replication of N. caninum tachyzoites within host cells is responsible for the acute phase of N. caninum infection. Evidence shows that the host immune response plays an essential role in recognizing and regulating the replication of invading pathogens. Nucleotide-binding oligomerization domain receptors (NLRs) are a class of cytoplasmic sensors that can sense pathogens and induce the formation of the inflammasome complex. Activation of the inflammasome promotes restriction of microbial replication. Our previous study revealed NLRP3 inflammasome activation in N. caninum-infected murine macrophages. However, the role of inflammasome activity in N. caninum-infected bovine cells is unknown. To address this question, a bovine peritoneal macrophage cell line was used to investigate the role of inflammasome activation in regulating intracellular N. caninum replication. The results showed that inflammasome mediated activation of caspase-1 occurs in N. caninum-infected bovine macrophages, and caspase-1-dependent cell death was considered to be induced in N. caninum-infected bovine macrophages because N. caninum induced cell death decreased following pretreatment with zVAD-fmk and VX765. Meanwhile, the inhibition of caspase-1 in N. caninum-infected bovine macrophages led to the presence of more parasites in the parasitophorous vacuole. In contrast, inflammasome activation induced by ATP treatment in N. caninum-infected bovine macrophages contributed to the clearance of N. caninum. In addition, pyroptotic cell supernatant collected from ATP-stimulated bovine macrophages also impaired the ability of this parasite to infect new cells. In conclusion, this study is the first report on the role of the bovine inflammasome in restraining intracellular N. caninum replication and suggests that the bovine inflammasome may be a potential target for future development of drugs or vaccines against N. caninum infection in cattle.

Keywords: Bovine macrophages; Inflammasome; Neospora caninum; Parasite replication.