Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from the blood of young and older HIV-negative and positive adults and stimulated with TDB (Trehalose-6,6-dibehenate) a synthetic analog of TDM. Multicolor flow cytometry was employed to evaluate intracellular cytokine production including: TNF-a, IL-10, IL-12, and IL-6. Monocytes were defined into subsets via expression of CD14, CD16, and CD11b. HIV positive individuals were recruited in the following age groups: 22 subjects (21-40 yrs), 29 subjects (50-64 yrs), and 14 subjects (65 years or older). These subjects were compared to a non-HIV control cohort of young (21-30 yrs) and older adults (≥ 65 years).
Results: Our preliminary studies show an age- and HIV-associated increase in IL-12 production in monocytes following stimulation with TDB, the Mincle ligand. Additionally, both age and HIV infection are associated with an increased proportion of monocytes producing multiple cytokines at the monocyte population level. The proportion of monocytes producing 2 or more cytokines was significantly increased in young HIV-positive adults, as compared to young HIV-negative adults (p=0.004), with a similar trend in older HIV-positive vs. negative adults. Boolean gating also demonstrated production of multiple cytokines, or multi-functionality at the single cell level. Of note, increased multi-functionality was associated with age and HIV infection in all monocyte subsets.
Conclusion: Monocyte multi-functionality may be a sign of age and HIV-associated immune dysregulation, and may provide insight into the increased reactivation of MTB seen in older adults and HIV-infected individuals.
S. Mohanty, None
J. Wilson, None
P. Van Ness, None
L. Han, None
L. Barakat, None
A. Shaw, None