The Role of Toll-Like Receptor 2 in the Recognition of Aggregatibacter actinomycetemcomitans

被引：29

作者：

Gelani, Valeria ^{[1
]}

Fernandes, Ana Paula ^{[1
]}

Gasparoto, Thais Helena ^{[1
]}

Garlet, Thiago Pompermaier ^{[2
]}

Cestari, Tania Mary ^{[1
]}

Lima, Hayana Ramos ^{[1
]}

Ramos, Erivan Schnaider, Jr. ^{[1
]}

de Souza Malaspina, Tatiana Salles ^{[1
]}

Santos, Carlos Ferreira ^{[1
]}

Garlet, Gustavo Pompermaier ^{[1
]}

da Silva, Joao Santana ^{[3
]}

Campanelli, Ana Paula ^{[1
]}

机构：

[1] Univ Sao Paulo, Dept Biol Sci, Bauru Sch Dent, BR-17012901 Bauru, SP, Brazil

[2] Univ Sao Paulo, Dept Pharmacol, Sch Med Ribeirao Preto, BR-14049 Ribeirao Preto, SP, Brazil

[3] Univ Sao Paulo, Dept Biochem & Immunol, Sch Med Ribeirao Preto, BR-14049 Ribeirao Preto, SP, Brazil

来源：

JOURNAL OF PERIODONTOLOGY | 2009年 / 80卷 / 12期

关键词：

Apoptosis; cytokines; neutrophils; periodontitis; phagocytosis; Toll-like receptors; INNATE IMMUNE-RESPONSE; CYTOLETHAL DISTENDING TOXIN; ACTINOBACILLUS-ACTINOMYCETEMCOMITANS; TISSUE DESTRUCTION; CANDIDA-ALBICANS; NECROSIS-FACTOR; CELL-DEATH; T-CELLS; BACTERIA; MICE;

D O I：

10.1902/jop.2009.090198

中图分类号：

R78 [口腔科学];

学科分类号：

1003 ;

摘要：

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-1 beta 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. Conclusion: The results of this study highlight the involvement of TLR2 in recognizing A. actinomycetemcomitans and its essential role in controlling A. actinomycetemcomitans infection. J Periodontot 2009,80:2070-2019.

引用

页码：2010 / 2019

页数：10

共 43 条

[1] Toll-like receptors in the induction of the innate immune response [J].

Aderem, A ;

Ulevitch, RJ .

NATURE, 2000, 406 (6797) :782-787

[2]

Albandar Jasim M, 2005, Dent Clin North Am, V49, P517, DOI 10.1016/j.cden.2005.03.003

[3] Specific primer for AP-PCR identification of Actinobacillus actinomycetemcomitans [J].

Avila-Campos, MJ ;

Sacchi, CT ;

Whitney, AM ;

Steigerwalt, AG ;

Mayer, LW .

JOURNAL OF CLINICAL PERIODONTOLOGY, 1999, 26 (11) :699-704

[4] Signalling mechanisms for Toll-like receptor-activated neutrophil exocytosis: key roles for interleukin-1-receptor-associated kinase-4 and phosphatidylinositol 3-kinase but not Toll/IL-1 receptor (TIR) domain-containing adaptor inducing IFN-β (TRIF) [J].

Brzezinska, Agnieszka A. ;

Johnson, Jennifer L. ;

Munafo, Daniela B. ;

Ellis, Beverly A. ;

Catz, Sergio D. .

IMMUNOLOGY, 2009, 127 (03) :386-397

[5]

CARPENTER A, 1995, J IMMUNOL, V155, P2005

[6] Cytolethal distending toxin generates cell death by inducing a bottleneck in the cell cycle [J].

Ceelen, LM ;

Decostere, A ;

Ducatelle, R ;

Haesebrouck, F .

MICROBIOLOGICAL RESEARCH, 2006, 161 (02) :109-120

[7] Nitric oxide-enhanced resistance to oral candidiasis [J].

Elahi, S ;

Pang, G ;

Ashman, RB ;

Clancy, R .

IMMUNOLOGY, 2001, 104 (04) :447-454

[8] Contribution of Toll-like receptors to the innate immune response to Gram-negative and Gram-positive bacteria [J].

Elson, Greg ;

Dunn-Siegrist, Irene ;

Daubeuf, Bruno ;

Pugin, Jerome .

BLOOD, 2007, 109 (04) :1574-1583

[9] Inhibition of interferon-γ-induced nitric oxide production in endotoxin-activated macrophages by cytolethal distending toxin [J].

Fernandes, K. P. S. ;

Mayer, M. P. A. ;

Ando, E. S. ;

Ulbrich, A. G. ;

Amarente-Mendes, J. G. P. ;

Russo, M. .

ORAL MICROBIOLOGY AND IMMUNOLOGY, 2008, 23 (05) :360-366

[10] The dual role of p55 turnour necrosis factor-α receptor in Actinobacillus actinomycetemcomitans-induced experimental periodontitis:: host protection and tissue destruction [J].

Garlet, G. P. ;

Cardoso, C. R. B. ;

Campanelli, A. P. ;

Ferreira, B. R. ;

Avila-Campos, M. J. ;

Cunha, F. Q. ;

Silva, J. S. .

CLINICAL AND EXPERIMENTAL IMMUNOLOGY, 2007, 147 (01) :128-138

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