This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Google Scholar
Right arrow Articles by Nussbaum, G.
Right arrow Articles by Rosen, G.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Nussbaum, G.
Right arrow Articles by Rosen, G.

 Previous Article  |  Next Article 

Infection and Immunity, September 2009, p. 3939-3947, Vol. 77, No. 9
0019-9567/09/$08.00+0     doi:10.1128/IAI.00488-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Involvement of Toll-Like Receptors 2 and 4 in the Innate Immune Response to Treponema denticola and Its Outer Sheath Components {triangledown}

Gabriel Nussbaum,* Shimon Ben-Adi, Tamar Genzler, Michael Sela, and Graciela Rosen

Institute of Dental Sciences, Faculty of Dental Medicine, Hadassah and Hebrew University Medical Center, Jerusalem, Israel

Received 3 May 2009/ Returned for modification 13 May 2009/ Accepted 7 July 2009

Treponema denticola is considered an important oral pathogen in the development and progression of periodontal diseases. In the present study, the mechanisms of recognition and activation of murine macrophages by T. denticola and its major outer sheath protein (MSP) and lipooligosaccharide (LOS or glycolipid) were investigated. T. denticola cells and the MSP induced innate immune responses through TLR2-MyD88, whereas LOS induced a macrophage response through TLR4-MyD88. The presence of gamma interferon (IFN-{gamma}), or of high numbers of T. denticola, circumvented the requirement for TLR2 for the macrophage response to T. denticola, although the response was still dependent on MyD88. In contrast, synergy with IFN-{gamma} did not alter the TLR dependence of the response to the T. denticola surface components LOS and MSP, despite enhanced sensitivity. These data suggest that although there is flexibility in the requirements for recognition of T. denticola cells (TLR2 dependent or independent), MyD88 is a requirement for the downstream signaling events that lead to inflammation. We also demonstrate that both outer sheath molecules LOS and MSP induce macrophage tolerance to further stimulation with enterobacterial lipopolysaccharide. Tolerance induced by T. denticola components during mixed infections may represent a general mechanism through which bacteria evade clearance.

* Corresponding author. Mailing address: Hebrew University-Hadassah Faculty of Dental Medicine, POB 12272, Jerusalem 91120, Israel. Phone: 972-2-6758581. Fax: 972-2-6758561. E-mail: gabrieln{at}ekmd.huji.ac.il

{triangledown} Published ahead of print on 13 July 2009.

Editor: A. J. Bäumler

Infection and Immunity, September 2009, p. 3939-3947, Vol. 77, No. 9
0019-9567/09/$08.00+0     doi:10.1128/IAI.00488-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»