Impact of Aging and HIV Infection on the Function of the C-Type Lectin Receptor MINCLE in Monocytes.

Both aging and HIV infection are associated with an enhanced pro-inflammatory environment that contributes to impaired immune responses and is mediated in part by innate immune pattern-recognition receptors. MINCLE is a C-type lectin receptor that recognizes trehalose 6,6,' di-mycolate (TDM) or "cord factor," the most abundant glycolipid in Mycobacterium tuberculosis (MTB). Here, we evaluated MINCLE function in monocytes in a cohort of HIV-infected and uninfected young (21-35) and older adults (60 years) via stimulation of PBMCs with TDB (Trehalose-6,6-dibehenate), a synthetic analog of TDM and measurement of cytokine production (IL-10, IL-12, IL-6, TNF-) by multicolor flow cytometry. Our studies show an age- and HIV-associated increase in cytokine multi-functionality of monocytes both at the population and single cell level that was dominated by IL-12, IL-10 and IL-6. These findings provide insight into the host response to MTB, and possible sources for the pro-inflammatory environment seen in aging and HIV infection.