title: The role of toll-like receptor 2 in the recognition of Aggregatibacter actinomycetemcomitans.
abstract: 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-deficient mice 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. A significantly diminished production of the cytokines tumor necrosis factor-alpha and interleukin-1beta 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 inflammatory exudates from TLR2(-/-) mice was observed. Phagocytosis and nitric oxide production was diminished in cells from TLR2(-/-) mice, facilitating the dissemination of the pathogen to the spleen.
  
  
  CONCLUSIONS
  The results of this study highlight the involvement of TLR2 in recognizing A. actinomycetemcomitans and its essential role in controlling A. actinomycetemcomitans infection.
authors: Department of Biological Sciences, Bauru School of Dentistry, University of São Paulo, Bauru, SP, Brazil.
authors: Valéria
authors: V
authors: Gelani
authors: Ana Paula
authors: AP
authors: Fernandes
authors: Thaís Helena
authors: TH
authors: Gasparoto
authors: Thiago Pompermaier
authors: TP
authors: Garlet
authors: Tânia Mary
authors: TM
authors: Cestari
authors: Hayana Ramos
authors: HR
authors: Lima
authors: Erivan Schnaider
authors: ES
authors: Ramos
authors: Tatiana Salles
authors: TS
authors: de Souza Malaspina
authors: Carlos Ferreira
authors: CF
authors: Santos
authors: Gustavo Pompermaier
authors: GP
authors: Garlet
authors: João Santana
authors: JS
authors: da Silva
authors: Ana Paula
authors: AP
authors: Campanelli
mesh_terms: D000189:Actinobacillus Infections / Q000276:immunology; D016976:Aggregatibacter actinomycetemcomitans / Q000276:immunology*; D016301:Alveolar Bone Loss / Q000276:immunology / Q000382:microbiology; D000818:Animals; D017209:Apoptosis / Q000276:immunology; D018946:Chemokine CCL5 / Q000032:analysis; D019742:Chemokines, CC / Q000032:analysis; D019743:Chemokines, CXC / Q000032:analysis; D002633:Chemotaxis / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D015169:Colony Count, Microbial; D053583:Interleukin-1beta / Q000032:analysis; D008264:Macrophages / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology; D009569:Nitric Oxide / Q000032:analysis; D010518:Periodontitis / Q000276:immunology / Q000382:microbiology; D010529:Peritoneal Cavity / Q000382:microbiology; D010587:Phagocytosis / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: C503460:Ccl5 protein, mouse; D018946:Chemokine CCL5; D019742:Chemokines, CC; D019743:Chemokines, CXC; D053583:Interleukin-1beta; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide