Toll-like receptor 2-mediated interleukin-8 expression in gingival epithelial cells by the Tannerella forsythia leucine-rich repeat protein BspA.
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.
Onishi
Shinsuke
S
Department of Oral Biology, School of Dental Medicine, University at Buffalo, State University of New York, 3435 Main St., Buffalo, NY 14214-3092, USA.
Honma
Kiyonobu
K
Liang
Shuang
S
Stathopoulou
Panagiota
P
Kinane
Denis
D
Hajishengallis
George
G
Sharma
Ashu
A
D001426:Bacterial Proteins / Q000494:pharmacology*; D002460:Cell Line; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism*; D005881:Gingiva / Q000166:cytology*; D006089:Gram-Negative Anaerobic Bacteria / Q000378:metabolism; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics* / Q000378:metabolism; D008565:Membrane Proteins / Q000494:pharmacology*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D051194:Toll-Like Receptor 1 / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000378:metabolism*; D051216:Toll-Like Receptor 6 / Q000378:metabolism
D001426:Bacterial Proteins; C105995:BspA protein, bacteria; D016209:Interleukin-8; D008565:Membrane Proteins; C495342:TLR2 protein, human; C495368:TLR6 protein, human; D051194:Toll-Like Receptor 1; D051195:Toll-Like Receptor 2; D051216:Toll-Like Receptor 6