Role of NOD2 and RIP2 in host-microbe interactions with Gram-negative bacteria: insights from the periodontal disease model

Autor(es)

Souza, Joao A. C. ; Medeiros, Marcell C. ; Rocha, Fernanda R. G. ; de Aquino, Sabrina G. ; Avila-Campos, Mario J. ; Spolidorio, Luis C. ; Zamboni, Dario S. ; Graves, Dana T. ; Rossa Junior, Carlos

• Tipo de documento: Artigo Científico
• Fonte: Innate Immunity; v. 22, n. 8, p. 598-611, NOV 2016.
• Citações Web of Science: 3

Resumo

NOD2 is a member of the NLR family of proteins that participate in the activation of the innate immune response. RIP2 is a downstream kinase activated by both NOD1 and NOD2. There is scarcity of information regarding the relevance of NOD2 in periodontitis, a chronic inflammatory condition characterized by inflammatory bone resorption. We used NOD2-KO and RIP2-KO mice in a model of microbial-induced periodontitis. Heat-killed Aggregatibacter actinomycetemcomitans was injected in the gingival tissues three times/wk for 4 wk. Bone resorption was assessed by CT analysis; osteoclasts were identified by immunohistochemical staining for TRAP and inflammation was assessed using a severity score system in H/E-stained sections. Invitro studies using primary macrophages assessed the response macrophages using qPCR-based array and multi-ligand ELISA. Bone resorption and osteoclastogenesis were significantly reduced in NOD2-KO mice. Severity of inflammation was not affected. qPCR-focused arrays and multi-ligand ELISA showed that expression of pro-inflammatory mediators was reduced in NOD2- and RIP2-deficient cells. RANKL-induced osteoclastogenesis was impaired in NOD2- and RIP2-deficient macrophages. We conclude that NOD2 is important for osteoclast differentiation and inflammatory bone resorption invivo and also for the macrophage response to Gram-negative bacteria. (AU)

• Processo FAPESP: 10/05783-5 - Papel das proteínas NOD na modulação da resposta imune nas doenças periodontais
• Beneficiário: Carlos Rossa Junior
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 10/05632-7 - Papel das proteínas Nod na modulação da resposta imune nas doenças periodontais
• Beneficiário: João Antonio Chaves de Souza
• Modalidade de apoio: Bolsas no Brasil - Doutorado