1. Nucleotide-binding oligomerization domain-containing protein 2 prompts potent inflammatory stimuli during Neospora caninum infection.
- Author
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Davoli-Ferreira M, Fonseca DM, Mota CM, Dias MS, Lima-Junior DS, da Silva MV, Quirino GF, Zamboni DS, Silva JS, and Mineo TW
- Subjects
- Animals, Cell Line, Cytokines metabolism, Disease Models, Animal, Female, Humans, Mice, Inbred C57BL, Mice, Knockout, Coccidiosis pathology, Host-Pathogen Interactions, Inflammation pathology, Macrophages immunology, Macrophages parasitology, Neospora immunology, Nod2 Signaling Adaptor Protein metabolism
- Abstract
Neospora caninum is an apicomplexan parasite responsible for major economic losses due to abortions in cattle. Innate immune responses are crucial for host resistance against the infection, however the molecules involved in parasite recognition are still poorly understood. Nod2 is a cytosolic receptor that recognizes several pathogens and its role during N. caninum infection has not yet been described. In that sense, we evaluated the role of Nod2 in host response against this parasite. We found that infection of macrophages induced increased expression of Nod2, which colocalized with the parasites' vacuoles. Nod2-deficient macrophages showed an impaired induction of pro-inflammatory cytokines, increased production of modulatory molecules, and failure to restrict parasite replication. In vivo, Nod2-knockout mice showed a reduction of MAPK phosphorylation and proinflammatory cytokines, followed by decreased inflammation in target organs and increment in parasite burden. Surprisingly, these mice were partially resistant to lethal doses of tachyzoites. In addition, these phenomena were not observed in Rip2-/- mice. In conclusion, our study indicates that Nod2-dependent responses account for N. caninum elimination. On the other hand, the inflammatory milieu induced by this innate receptor provoked pathogenesis and death in severe experimental neosporosis.
- Published
- 2016
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