title: Nucleotide-binding oligomerization domain-containing protein 2 prompts potent inflammatory stimuli during Neospora caninum infection.
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.
authors.affiliation: Laboratory of Immunoparasitology "Dr. Mário Endsfeldz Camargo", Institute of Biomedical Sciences, Federal University of Uberlândia, Uberlândia, Minas Gerais, Brazil.|Department of Biochemistry and Immunology, Ribeirão Preto, School of Medicine, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Marcela
authors.initials: M
authors.lastname: Davoli-Ferreira
authors.affiliation: Department of Biochemistry and Immunology, Ribeirão Preto, School of Medicine, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.|Program in Barrier Immunity and Repair, Mucosal Immunology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Disease (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA.
authors.forename: Denise M
authors.initials: DM
authors.lastname: Fonseca
authors.affiliation: Laboratory of Immunoparasitology "Dr. Mário Endsfeldz Camargo", Institute of Biomedical Sciences, Federal University of Uberlândia, Uberlândia, Minas Gerais, Brazil.
authors.forename: Caroline M
authors.initials: CM
authors.lastname: Mota
authors.affiliation: Department of Biochemistry and Immunology, Ribeirão Preto, School of Medicine, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Murilo S
authors.initials: MS
authors.lastname: Dias
authors.affiliation: Department of Biochemistry and Immunology, Ribeirão Preto, School of Medicine, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Djalma S
authors.initials: DS
authors.lastname: Lima-Junior
authors.affiliation: Laboratory of Immunoparasitology "Dr. Mário Endsfeldz Camargo", Institute of Biomedical Sciences, Federal University of Uberlândia, Uberlândia, Minas Gerais, Brazil.
authors.forename: Murilo V
authors.initials: MV
authors.lastname: da Silva
authors.affiliation: Department of Biochemistry and Immunology, Ribeirão Preto, School of Medicine, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Gustavo F S
authors.initials: GF
authors.lastname: Quirino
authors.affiliation: Department of Cell Biology, Ribeirão Preto, School of Medicine, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Dario S
authors.initials: DS
authors.lastname: Zamboni
authors.affiliation: Department of Biochemistry and Immunology, Ribeirão Preto, School of Medicine, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: João S
authors.initials: JS
authors.lastname: Silva
authors.affiliation: Laboratory of Immunoparasitology "Dr. Mário Endsfeldz Camargo", Institute of Biomedical Sciences, Federal University of Uberlândia, Uberlândia, Minas Gerais, Brazil.
authors.forename: Tiago W P
authors.initials: TW
authors.lastname: Mineo
mesh_terms: D000818:Animals; D002460:Cell Line; D003048:Coccidiosis / Q000473:pathology*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D054884:Host-Pathogen Interactions; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D008264:Macrophages / Q000276:immunology* / Q000469:parasitology*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018688:Neospora / Q000276:immunology*; D053473:Nod2 Signaling Adaptor Protein / Q000378:metabolism*
chemical_list: D016207:Cytokines; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein