Variability in the response of human dendritic cells stimulated with Porphyromonas gingivalis or Aggregatibacter actinomycetemcomitans

9 páginas, 4 figuras, 1 tabla -- PAGS nros. 689-697Background and Objective: Dendritic cells are able to prime and polarize naïve T cells towards either a T helper 1 or a T helper 2 response, depending on the antigen type and concentration, the costimulatory signals and the local cytokine millieu. In this investigation, we analyzed the response of human dendritic cells to stimulation with different concentrations of Porphyromonas gingivalis or Aggregatibacter actinomycetemcomitans. Material and Methods: Using different concentrations of P. gingivalis ATCC 33277 and A. actinomycetemcomitans ATCC 33384, we determined the expression of the maturation markers CD80 and CD86 from purified human dendritic cells by flow cytometry. We also evaluated the mRNA expression levels for the cytokines interleukin-1β, interleukin-2, interleukin-5, interleukin-6, interleukin-10, interleukin-12, interleukin-13, interferon-γ, tumor necrosis factor-α and tumor necrosis factor-β by quantitative real-time reverse transcription–polymerase chain reaction. Results: Both P. gingivalis and A. actinomycetemcomitans led to dendritic cell maturation, but the expression of CD80 was higher when the dendritic cells were stimulated with A. actinomycetemcomitans. Although both pathogens induced a T helper 1 pattern of cytokine expression, A. actinomycetemcomitans-stimulated dendritic cells expressed interleukin-1β, interleukin-12, interferon-γ, tumor necrosis factor-α and tumor necrosis factor-β at lower bacterial concentrations than P. gingivalis. While 106 bacteria/mL of P. gingivalis or 104 bacteria/mL of A. actinomycetemcomitans induced expression of interleukin-12p40, the expression of other cytokines required 10 to 100-fold higher concentrations of bacteria. Conclusion: These results demonstrate that A. actinomycetemcomitans is a more potent immunogen than P. gingivalis because, at least in vitro, it induces stronger differentiation and activation of dendritic cells. In addition, our data also show that for a given strain, the bacterial load determines the pattern of cytokines that are expressedThe work in the author’s laboratories has been supported by grant from the Spanish Ministry of Health (FIS-060181 to MS), Spanish Ministry of Science and Education (SAF2006-4826 and SAF2006-04903 to AS and JAGS, respectively) and Chilean Government (CONICYT-26080046 to RV)Peer reviewe