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

• Autor(a) principal: Souza, Joao A.C. [UNESP]
• Data de Publicação: 2016
• Outros Autores: Medeiros, Marcell C. [UNESP], Rocha, Fernanda R.G. [UNESP], De Aquino, Sabrina G. [UNESP], Ávila-Campos, Mario J., Spolidorio, Luis C. [UNESP], Zamboni, Dario S., Graves, Dana T., Rossa, Carlos [UNESP]
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UNESP
• Texto Completo: http://dx.doi.org/10.1177/1753425916666652; http://hdl.handle.net/11449/173651
• topic: Bone resorption; inflammation; innate immunity; macrophages; NOD2 signaling adaptor protein

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 μCT analysis; osteoclasts were identified by immunohistochemical staining for TRAP and inflammation was assessed using a severity score system in H/E-stained sections. In vitro 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 in vivo and also for the macrophage response to Gram-negative bacteria.