HAART regimens have modified HIV diseases, with longer survival rates and improved quality of life. However, complete eradication of HIV has not been achieved with currently available HAART regimens, since immune cells including immature (iDC) and mature dendritic cells (mDCs) can serve as an HIV reservoir, constituting a major obstacle to controlling HIV infections. Both exogenous and endogenous stimuli, e.g. Gram negative bacteria, LPS, and host factors, have been shown to reactivate HIV-1 infections. OBJECTIVE: Since periodontal disease is a chronic bacterial infection, this study evaluated the ability of oral microorganisms to activate HIV-1 in latently infected DCs. METHODS: The THP-1 cell line was driven to an iDC phenotype by treatment with GM-CSF/IL-4. TNFa was then used to cause maturation of iDCs to mDCs. An LTR promoter-luciferase construct was used as the reporter for the HIV reactivation. The iDCs and mDCs were treated with various oral bacteria, e.g. P. gingivalis, F. nucleatum, C. rectus, S. mutans, and P. intermedia to activate the HIV promoter. RESULTS: Variations were observed among the bacterial stimuli in their ability to trigger HIV activation in iDCs and mDCs. Generally, oral bacteria could stimulate the HIV reactivation in iDCs; however, the stimulation was elevated in mDCs. C. rectus and S. mutans could stimulate HIV promoter activation equally well in iDCs and mDCs, while P. gingivalis, F. nucleatum, and P. intermedia had higher stimulation in mDCs than in the iDCs. CONCLUSIONS: An HIV-latently infected iDC and mDC cell line was established and used to determine the capacity of oral bacteria to reactivate HIV. The data support the hypothesis that oral bacteria associate with chronic periodontal infections can trigger latently infected DCs, contributing to HIV recrudescence and undermining HAART therapy. Supported by P20 RR020145.

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