Macrophage Responses to a Polymicrobial Challenge With Oral Bacteria

Periodontitis is a polymicrobial infection that elicits a chronic immunoinflammatory response resulting in destruction of host tissues.  Macrophages (mf) are critical for interacting with various microbes to enable antigen processing and presentation, and contribute to innate immunity and wound healing processes.  Moreover, this cell type has been shown to be a target of HIV infection and latency.  Objective:  This study examined polymicrobial activation of the HIV promoter and cytokine production in a model of HIV-latently infected macrophages (BF24). Methods: BF24 were grown for 3 days and treated with various combinations of oral microbial extracts (eg. P. gingivalis, A. actinomycetemcomitans, T. denticola, S. mutans, C. albicans, P. intermedia). CAT activities (HIV promoter activation) and levels of TNFa produced by the BF24 cells were measured.  Results: The mf reacted to certain combinations of polymicrobial challenge.  A significant synergistic response was observed in CAT production with an Aa/Pg combination compared to the individual bacteria.  An additive effect in promoter activation was observed with Aa/Pi and Aa/Ca. The polymicrobial challenge effect on CAT activity was dose-dependent and the synergistic effect was observed only at low dosages of the extracts.  A similar synergistic effect on TNFa production was also observed with the Aa/Pg combination. As with CAT induction, the polymicrobial challenge effect on cytokine production was dose-dependent, with the synergistic interactions observed only at low dosages.  Conclusions: Variations in the magnitude of macrophage responses supported unique features of the response profile to a polymicrobial challenge.  Both additive and synergistic response patterns to the polymicrobial challenge were observed.  The synergism was noted at low doses of the microbial stimuli, while the additive effects were generally observed at high doses. These data suggest that synergistic effects can only be demonstrated when the receptors for the microbial ligands on the macrophages remain unsaturated.  Supported by P20 RR020145.