804. Dendritic Cells From HIV-Positive Subjects Demonstrate Increased TNF-α and CCR7 Expression Following Mycobacterial Stimulation in a Whole Blood Ex Vivo Assay
Session: Abstracts: Oral Abstract Session: HIV Complications and Pathogenesis
Friday, October 22, 2010: 2:30 PM
Background:   Rates of active tuberculosis increase early in HIV infection before substantial declines in CD4+ T cell counts result in increased susceptibility to other opportunistic infections.  Early alteration in innate immune responses to mycobacteria following HIV infection may contribute to reactivation of tuberculosis. 

Methods:  Utilizing an ex vivo whole blood assay we assessed dendritic cell (DC) functional responses to mycobacterial stimulation (Mycobacterium bovis BCG) in 11 viremic and 12 HAART treated, aviremic HIV-positive individuals as well as 10 HIV-negative controls. Resiquimod (RSQ), a pharmacological TLR7/8 stimulus, was used as a comparator.  Following stimulation, cells were stained with monoclonal antibodies for DC identification (lin-1, HLA-DR, CD11c, CD123), cell surface activation markers (CCR7, CD80) and intracellular cytokines (IFN-α, TNF-α).  Analysis was performed by flow cytometry. Mean fluorescence intensity and/or percentage of cells expressing cytokine by intracellular staining were determined. 

Results:  TNF-α secretion in response to BCG was significantly increased in myeloid DCs from HIV-positive subjects compared with controls (p=0.021).  IFN-α was not detected in significant quantities following BCG stimulation. Myeloid DC CCR7 expression at baseline as well as with BCG stimulation was significantly increased in viremic patients compared with controls (p=0.05 for baseline and p=0.006 for BCG stimulated).   CD80 expression was increased in viremic subjects at baseline compared with aviremic and HIV negative controls (p<0.001).  For all markers evaluated, viremic subjects exhibited a trend toward increased expression when compared with aviremic HIV-positive subjects and HIV-negative controls.

Conclusion:  In a whole blood, ex vivo system, per-cell cytokine secretion and maturation marker expression in response to BCG stimulation was not diminished in DCs from HIV-positive individuals. Presence of HIV viremia appears to increase baseline DC activation and augment TNF-α and CCR7 responses to BCG in a whole blood ex vivo assay.   Abnormal dendritic cell activation following mycobacterial stimulation may promote increased susceptibility to tuberculosis following HIV infection.

Subject Category: E. Innate and adaptive immunity to infections, including vaccine immunology

Shayla Hesse , University of Miami School of Medicine, Miami, FL
Savita Pahwa, MD , Microbiology and Immunology, University of Miami School of Medicine, Miami, FL
Susanne Doblecki-Lewis, M.D. , Department of Medicine, Division of Infectious Diseases, University of Miami, Miami, FL


S. Hesse, None

S. Pahwa, None

S. Doblecki-Lewis, None

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