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Infection and Immunity, December 2007, p. 5763-5768, Vol. 75, No. 12
0019-9567/07/$08.00+0     doi:10.1128/IAI.01117-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Treponema denticola Activates Mitogen-Activated Protein Kinase Signal Pathways through Toll-Like Receptor 2{triangledown}

John Ruby,1* Kunal Rehani,2 and Michael Martin2

Department of Pediatric Dentistry, School of Dentistry, The University of Alabama at Birmingham, Birmingham, Alabama 35294,1 Department of Microbiology and Immunology, School of Dentistry, University of Louisville, Louisville, Kentucky 402022

Received 10 August 2007/ Returned for modification 4 September 2007/ Accepted 25 September 2007

Treponema denticola, a spirochete indigenous to the oral cavity, is associated with host inflammatory responses to anaerobic polymicrobial infections of the root canal, periodontium, and alveolar bone. However, the cellular mechanisms responsible for the recognition of T. denticola by the innate immune system and the underlying cell signaling pathways that regulate the inflammatory response to T. denticola are currently unresolved. In this study, we demonstrate that T. denticola induces innate immune responses via the utilization of Toll-like receptor 2 (TLR2) but not TLR4. Assessment of TLR2/1 and TLR2/6 heterodimers revealed that T. denticola predominantly utilizes TLR2/6 for the induction of cellular responses. Analysis of the mitogen-activated protein kinase (MAPK) signaling pathway in T. denticola-stimulated monocytes identified a prolonged up-regulation of the MAPK extracellular signal-related kinase 1/2 (ERK1/2) and p38, while no discernible increase in phospho-c-Jun N-terminal kinase 1/2 (JNK1/2) levels was observed. With the aid of pharmacological inhibitors selectively targeting ERK1/2 via the mitogen-activated protein kinase/extracellular signal-related kinase 1/2 kinase and p38, we further demonstrate that ERK1/2 and p38 play a major role in T. denticola-mediated pro- and anti-inflammatory cytokine production.

* Corresponding author. Mailing address: Department of Pediatric Dentistry, School of Dentistry, SDB 314, 1530 3rd Ave. S., The University of Alabama at Birmingham, Birmingham, AL 35294-0007. Phone: (205) 975-7003. Fax: (205) 975-5737. E-mail: john_ruby{at}cs1.dental.uab.edu

{triangledown} Published ahead of print on 8 October 2007.

Editor: A. J. Bäumler

Infection and Immunity, December 2007, p. 5763-5768, Vol. 75, No. 12
0019-9567/07/$08.00+0     doi:10.1128/IAI.01117-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Nussbaum, G., Ben-Adi, S., Genzler, T., Sela, M., Rosen, G. (2009). Involvement of Toll-Like Receptors 2 and 4 in the Innate Immune Response to Treponema denticola and Its Outer Sheath Components. Infect. Immun. 77: 3939-3947 [Abstract] [Full Text]  
  • Lee, S. F., Andrian, E., Rowland, E., Marquez, I. C. (2009). Immune Response and Alveolar Bone Resorption in a Mouse Model of Treponema denticola Infection. Infect. Immun. 77: 694-698 [Abstract] [Full Text]  


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