Toll-like receptor 2-mediated interleukin-8 expression in gingival epithelial cells by the Tannerella forsythia leucine-rich repeat protein BspA

Kiyonobu Honma Shinsuke Onishi, Shuang Liang, Panagiota Stathopoulou, Denis Kinane, George Hajishengallis, Ashu Sharma

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

Abstract

Tannerella forsythia is a gram-negative anaerobe strongly associated with chronic human periodontitis. This bacterium expresses a cell surface-associated and secreted protein, designated BspA, which has been recognized as an important virulence factor. The BspA protein belongs to the leucine-rich repeat (LRR) and bacterial immunoglobulin-like protein families. BspA is, moreover, a multifunctional protein which interacts with a variety of host cells, including monocytes which appear to respond to BspA through Toll-like receptor (TLR) signaling. Since gingival epithelium forms a barrier against periodontal pathogens, this study was undertaken to determine if gingival epithelial cells respond to BspA challenge and if TLRs play any role in BspA recognition. This study was also directed towards identifying the BspA domains responsible for cellular activation. We provide direct evidence for BspA binding to TLR2 and demonstrate that the release of the chemokine interleukin-8 from human gingival epithelial cells by BspA is TLR2 dependent. Furthermore, the LRR domain of BspA is involved in activation of TLR2, while TLR1 serves as a signaling partner. Thus, our findings suggest that BspA is an important modulator of host innate immune responses through activation of TLR2 in cooperation with TLR1.

Original languageEnglish (US)
Pages (from-to)198-205
Number of pages8
JournalInfection and Immunity
Volume76
Issue number1
DOIs
StatePublished - Jan 2008
Externally publishedYes

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

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