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

Heidi J Zapata1, Peter H Van Ness2, Stefan Avey3

  • 1Section of Infectious Diseases, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut.

Insights

Aging and HIV infection increase monocyte inflammatory responses, particularly involving interleukin-12, interleukin-10, and interleukin-6. This enhanced cytokine multifunctionality impacts immune function in both conditions.

Area of Science:

  • Immunology
  • Infectious Diseases
  • Aging Research

Background:

  • Aging and HIV infection are linked to increased inflammation, impairing immune responses.
  • Innate immune pattern-recognition receptors play a role in this pro-inflammatory environment.
  • The C-type lectin receptor MINCLE recognizes Mycobacterium tuberculosis glycolipids.

Purpose of the Study:

  • To evaluate MINCLE receptor function in monocytes from HIV-infected and uninfected individuals across different age groups.
  • To investigate the impact of aging and HIV on monocyte cytokine production.

Main Methods:

  • Peripheral blood mononuclear cells were stimulated with trehalose-6,6-dibehenate, a MINCLE ligand.
  • Cytokine production (IL-10, IL-12, IL-6, TNF-α) was measured using multicolor flow cytometry.
  • Monocyte cytokine multifunctionality was assessed at both population and single-cell levels.

Main Results:

  • An age- and HIV-associated increase in monocyte cytokine multifunctionality was observed.
  • This increase was predominantly characterized by elevated levels of IL-12, IL-10, and IL-6.
  • Findings were consistent at both population and single-cell analyses.

Conclusions:

  • Monocyte responses to MINCLE stimulation are altered in aging and HIV infection.
  • Increased IL-12, IL-10, and IL-6 production by monocytes contributes to the pro-inflammatory state in these conditions.
  • These findings offer insights into host responses to M. tuberculosis and the inflammatory milieu of aging and HIV.

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