Background: Aggregatibacter actinomycetemcomitans (previously Actinobacillus actinomycetemcomitans) is a Gram-negative bacterium present in the oral cavity and is usually associated with localized aggressive periodontitis. Isolated antigens from A. actinomycetemcomitans can activate innate immune cells through Toll-like receptors (TLRs), which are molecules that recognize structural components conserved among microorganisms. In this study, we evaluate the role of TLR2 in the recognition of A. actinomycetemcomitans. Methods: Macrophages and neutrophils from knockout mice with targeted disruption of TLR2 (TLR2 -/- mice) and wild-type mice were collected and used for the subsequent assays. The production of cytokines and chemokines was evaluated by enzyme-linked immunosorbent assay (ELISA), and the presence of apoptotic cells was determined by flow cytometry. In addition, the mechanisms that modulate the outcome of A. actinomycetemcomitans-induced periodontal disease in TLR2 -/- mice were examined. Results: The results show that TLR2-deficientmice developed more severe periodontitis after A. actinomycetemcomitans infection, characterized by significantly higher bone loss and inflammatory cell migration to periodontal tissues. The inflammatory cell influx into the peritoneal cavities of TLR2 -/- mice was three-fold lower than that observed for the littermate controls.Asignificantly diminished production of the cytokines tumor necrosis factor-alpha and interleukin-1β as well as the chemokine CC-ligand-5 in the peritoneal cavities of TLR2 -/- mice was observed. In addition, a high frequency of apoptotic cells in the inflammatoryexudates fromTLR2 -/- micewasobserved. Phagocytosis and nitric oxide production was diminished in cells from TLR2 -/- mice, facilitating the dissemination of the pathogen to the spleen. Conclusion: The results of this study highlight the involvment of TLR2 in recognizing A. actinomycetemcomitans and its essential role in controlling A. actinomycetemcomitans infection. J Periodontol 2009;80:2010-2019.
- Toll-like receptors
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