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

J Gerontol A Biol Sci Med Sci. 2019 May 16;74(6):794-801. doi: 10.1093/gerona/gly209.

Abstract

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'-dimycolate or "cord factor," the most abundant glycolipid in Mycobacterium tuberculosis. Here, we evaluated MINCLE function in monocytes in a cohort of HIV-infected and uninfected young (21-35 years) and older adults (≥60 years) via stimulation of peripheral blood mononuclear cells with trehalose-6,6-dibehenate, a synthetic analog of trehalose-6,6'-dimycolate and measurement of cytokine production (interleukin [IL]-10, IL-12, IL-6, tumor necrosis factor-α) by multicolor flow cytometry. Our studies show an age- and HIV-associated increase in cytokine multifunctionality 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 M. tuberculosis and possible sources for the pro-inflammatory environment seen in aging and HIV infection.

Keywords: Immune; Innate; Multifunctional; TDB.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aging / immunology*
  • Cohort Studies
  • Cytokines / metabolism
  • Female
  • Flow Cytometry
  • HIV Infections / immunology*
  • Humans
  • Lectins, C-Type / metabolism*
  • Male
  • Middle Aged
  • Monocytes / metabolism*
  • Receptors, Immunologic / metabolism*
  • Young Adult

Substances

  • CLEC4D protein, human
  • Cytokines
  • Lectins, C-Type
  • Receptors, Immunologic