Activation of toll-like receptors 2 and 4 by gram-negative periodontal bacteria.
OBJECTIVE
Periodontitis is a chronic infectious disease associated with a gram-negative subgingival microflora. Bacterial components stimulate, among other receptors, Toll-like receptor (TLR) 2 and/or TLR4. Accumulating evidence indicates that both qualitatively and quantitatively distinct immune responses result from the triggering of TLR2 as compared to TLR4 triggering. The aim was to study the interaction of Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans, Tannerella forsythensis, Prevotella intermedia, Prevotella nigrescens, Fusobacterium nucleatum and Veillonella parvula with TLR2 and TLR4. We investigated all known serotypes (K(-), K1-K6) of P. gingivalis and A. actinomycetemcomitans serotype a-e strains for their potency to stimulate cytokine production.


METHODS
Human embryonic kidney (HEK) cells, stably transfected with CD14, CD14-TLR2, or CD14-TLR4 and whole blood were stimulated with bacterial sonicates. Cytokine production (interleukin-6, -8, -10 and -12) was measured in the supernatant by enzyme-linked immunosorbent assay.


RESULTS
All test bacteria stimulated HEK-CD14-TLR2, but only A. actinomycetemcomitans and V. parvula stimulated HEK-CD14-TLR4. No differences were found in the activation of HEK-CD14-TLR2/4, or cytokine production in whole blood between serotypes of P. gingivalis and A. actinomycetemcomitans.


CONCLUSIONS
Gram-negative periodontal bacteria predominantly stimulated TLR2, which may be of importance for the Th1/Th2 cell orientation of the immune response in periodontitis.
Kikkert
R
R
Department of Immunopathology, Sanquin Research, Amsterdam, and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, The Netherlands. r.kikkert@sanquin.nl
Laine
M L
ML
Aarden
L A
LA
van Winkelhoff
A J
AJ
D016976:Aggregatibacter actinomycetemcomitans / Q000276:immunology; D002478:Cells, Cultured; D006090:Gram-Negative Bacteria / Q000276:immunology*; D006801:Humans; D007378:Interleukins / Q000096:biosynthesis / Q000097:blood; D010518:Periodontitis / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D016966:Porphyromonas gingivalis / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000276:immunology*; D014774:Virulence
D007378:Interleukins; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4