Kinin danger signals proteolytically released by gingipain induce Fimbriae-specific IFN-gamma- and IL-17-producing T cells in mice infected intramucosally with Porphyromonas gingivalis.

Porphyromonas gingivalis, a Gram-negative bacterium that causes periodontitis, activates the kinin system via the cysteine protease R-gingipain. Using a model of buccal infection based on P. gingivalis inoculation in the anterior mandibular vestibule, we studied whether kinins released by gingipain may link mucosal inflammation to T cell-dependent immunity through the activation of bradykinin B(2) receptors (B(2)R). Our data show that P. gingivalis W83 (wild type), but not gingipain-deficient mutant or wild-type bacteria pretreated with gingipain inhibitors, elicited buccal edema and gingivitis in BALB/c or C57BL/6 mice. Studies in TLR2(-/-), B(2)R(-/-), and neutrophil-depleted C57BL/6 mice revealed that P. gingivalis induced edema through the sequential activation of TLR2/neutrophils, with the initial plasma leakage being amplified by gingipain-dependent release of vasoactive kinins from plasma-borne kininogens. We then used fimbriae (Fim) Ag as a readout to verify whether activation of the TLR2-->PMN-->B(2)R axis (where PMN is polymorphonuclear neutrophil) at early stages of mucosal infection had impact on adaptive immunity. Analyzes of T cell recall responses indicated that gingipain drives B(2)R-dependent generation of IFN-gamma-producing Fim T cells in submandibular draining lymph nodes of BALB/c and C57BL/6 mice, whereas IL-17-producing Fim T cells were generated only in BALB/c mice. In summary, our studies suggest that two virulence factors, LPS (an atypical TLR2 ligand) and gingipain, forge a trans-cellular cross-talk between TLR2 and B(2)R, thus forming an innate axis that guides the development of Fim-specific T cells in mice challenged intrabuccally by P. gingivalis. Ongoing research may clarify whether kinin-driven modulation of T cell responses may also influence the severity of chronic periodontitis.

Relação entre o tratamento periodontal e o controle metabólico do diabetes mellitus: revisão de literatura / The relationship between periodontal treatment and metabolic control of diabetes mellitus: a review of literature

Diabetes Mellitus (DM) é uma doença metabólica devido a alterações na produção de insulina ou resistência tecidual à mesma, levando a alteração no metabolismo de lipídeos, de açúcares e de proteína. A hiperglicemia resultante pode induzir diversas patologias de sistemas orgânicos. Por sua vez, a Doença Periodontal (DP) promove um desafio bacteriano constante, o que gera maior atividade de monócitos/macrófagos, aumentando a secreção de citocinas pró-inflamatórias. Em estados hiperglicêmicos, existe a formação de produtos finais de glicação avançada (AGEs). O acúmulo nos tecidos de AGEs em diabéticos gera uma resposta hiperinflamatória. Esses fatores, em conjunto, levam a uma alteração na resposta imuno-inflamatóriado hospedeiro, gerando uma menor resistência à infecção e capacidade reparadora. Sendo assim, a terapia periodontal, através do controle do biofilme dental a níveis compatíveis com saúde, reduz a carga microbiana local e,conseqüentemente, diminui os desafios metabólicos nestes indivíduos. Assim, o objetivo deste trabalho, foi revisar os mecanismos pelos quais a DP, bem como a sua terapia associada ou não ao uso de antimicrobianos sistêmicos, podem atuar sobre o controle sistêmico do DM. Conclui-se que, apesar de existir discordância na literatura, os periodontistas deveriam atuar de forma educativa com seus pacientes e seus médicos alertando para a relação entre DP e DM.

Diabetes Mellitus (DM) is a metabolic disease due to alterations in the production of insulin or tissue resistance to it, leading to abnormal fat, sugar, and protein metabolism. Resultant hyperglycemia can induce diverse multiple systems pathologies. On the other hand, periodontal disease (PD)promotes a constant bacterial challenge, which increases monocyte/macrophage activity, and pro-inflammatory cytokines secretion. In hyperglycemic states, there is advanced glycation end-products (AGEs) production. In diabetic subjects, the AGEs accumulation in the tissue leads to a hyper-inflammatory response, generating po or resistance to infections and impaired wound healing. There fore, periodontal therapy, through dental biofilm control, decreases the microbial load and, as a consequence, reduces the metabolic challenges in those subjects. The present paper aims to review the mechanisms through what periodontal disease and its treatment, associated or not to systemic antibiotics, can affect systemic control of DM. It was concluded that despite the existing lack of agreement in the studied literature, periodontists should warn their patients and their doctors about the relationship between PD and DM.