2192. Effect of Aging and HIV Infection on the Function of Mincle, an Innate Immune Receptor for Cord Factor from M. Tuberculosis
Session: Poster Abstract Session: Host-Pathogen Interactions
Saturday, October 29, 2016
Room: Poster Hall
Background: Both aging and HIV infection are associated with an enhanced pro-inflammatory environment that may contribute to increased morbidity and mortality from infections. This pro-inflammatory environment reflects innate inflammatory dysregulation, mediated by pattern recognition receptors (PRRs) such as Toll-like receptors (TLRs). Mincle is a member of the C-type lectin receptors, a family of PRRs that recognize carbohydrate motifs. Specifically, Mincle is the receptor for trehalose 6,6’ di-mycolate (TDM) or “cord factor,” the most abundant glycolipid in Mycobacterium tuberculosis (MTB).

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.

Heidi Zapata, MD., PhD.1, Barbara Siconolfi, BSN, RN2, Subhasis Mohanty, PhD2, Jean Wilson, BA3, Peter Van Ness, PhD, MPH4, Ling Han, MD, PhD5, Lydia Barakat, MD2 and Albert Shaw, MD, PhD, FIDSA6, (1)Infectious Disease, Yale University School of Medicine, New Haven, CT, (2)Yale University School of Medicine, New Haven, CT, (3)Infectious Diseases, Yale University School of Medicine, New Haven, CT, (4)Department of Internal Medicine, Section of Geriatrics, Yale School of Medicine, New Haven, CT, (5)Geriatrics, Yale University, New Haven, CT, (6)Yale University, New Haven, CT

Disclosures:

H. Zapata, None

B. Siconolfi, None

S. Mohanty, None

J. Wilson, None

P. Van Ness, None

L. Han, None

L. Barakat, None

A. Shaw, None

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