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Role of NOD proteins in the modulation of the immune response in periodontal diseases


Recognition of pathogenic bacteria by the host is initially mediated by the innate immune response through detection of pathogen-associated molecular patterns (PAMPs) by Toll-like receptors (TLR) and Nucleotide-oligomerization domain (Nod) proteins. Since the oral cavity as well as other mucosal surfaces, is continuously colonized with non-pathogenic bacteria that also present PAMPs, there has to be an endogenous negative regulatory mechanism in place to prevent an overt host response with deleterious consequences. Specifically in the oral mucosa, it is not clear how the immune system is able to quickly distinguish between commensal and pathogenic bacteria and tailor the host response. Nod proteins were initially described as 'intracellular TLRs' that recognize PAMPs associated with bacteria invading the cytosol; however these proteins have been shown to modulate the activation of various signaling pathways involved in the expression of inflammatory genes, including p38 MAPK and NF-ºB in concert with TLR stimulation. We have found that Nod proteins are required for transcriptional activation of RANKL mediated by TLR signaling, suggesting a potential role of these proteins in inflammation and on the bone resorption associated with infectious conditions. However, there is paucity of information on the in vivo role of Nod proteins in the modulation of host-microbe interactions in the oral mucosa. Based on this information, our hypothesis is that Nod proteins play an important role in the modulation of the inflammatory reaction associated with periodontal diseases and its consequences, including alveolar bone resorption. To test this hypothesis, we propose the following specific aims: Specific Aim #1: Assess the role of Nod proteins in the inflammation and bone resorption in experimentally-induced periodontal disease; Specific Aim #2: Describe the influence of Nod proteins on the cytokine and signaling networks associated with periodontal disease (AU)

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(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
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. Role of NOD2 and RIP2 in host-microbe interactions with Gram-negative bacteria: insights from the periodontal disease model. Innate Immunity, v. 22, n. 8, p. 598-611, . (10/05783-5, 10/05632-7)
CHAVES DE SOUZA, JOAO ANTONIO; TFAILE FRASNELLI, SABRINA CRUZ; CURYLOFO-ZOTTI, FABIANA DE ALMEIDA; AVILA-CAMPOS, MARIO JULIO; SPOLIDORIO, LUIS CARLOS; ZAMBONI, DARIO SIMOES; GRAVES, DANA T.; ROSSA, JR., CARLOS. NOD1 in the modulation of host-microbe interactions and inflammatory bone resorption in the periodontal disease model. Immunology, v. 149, n. 4, p. 374-385, . (10/05783-5, 10/05632-7)

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