Galectin-3, Galectin-9, and Interleukin-18 Are Associated with Monocyte/Macrophage Activation and Turnover More so than Simian Immunodeficiency Virus-Associated Cardiac Pathology or Encephalitis

AIDS Res Hum Retroviruses. 2024 Sep;40(9):531-542. doi: 10.1089/AID.2024.0008. Epub 2024 Jun 12.

Abstract

Despite antiretroviral therapy (ART), people living with HIV (PLWH) are at increased risk of developing cardiovascular disease (CVD) and HIV-associated neurocognitive disorder (HAND), among other comorbidities. Studies from ART-treated individuals identified galectin-3 (gal-3) and interleukin (IL)-18 as CVD biomarkers, galectin-9 (gal-9) as a HAND biomarker, and sCD163, a marker of monocyte/macrophage activation, as a biomarker of both. We asked if plasma gal-3, gal-9, and IL-18 are associated with an individual comorbidity or increase in both with animals that develop AIDS with both pathologies versus (CVD-path) alone or simian immunodeficiency virus encephalitis (SIVE) alone. We found that no biomarkers were selective between individual pathologies, and all biomarkers increased with co-development of CVD-path and SIVE (gal-3, p = 0.11; gal-9, p = 0.001; IL-18, p = 0.007; sCD163, p < 0.001; %BrdU p = 0.02). Although gal-3, gal-9, and IL-18 did not distinguish between pathologies, they correlated strongly with one another, with sCD163, a marker of monocyte/macrophage activation, and the %BrdU monocytes, a marker of monocyte turnover. Compared to animals with CVD-path or SIVE alone, animals that co-developed both pathologies had consistently elevated IL-18 throughout infection (p = 0.02) and increased sCD163 in late infection (p = 0.01). These data indicate that gal-3, gal-9, and IL-18 are associated with monocyte/macrophage activation by sCD163 and monocyte turnover by the %BrdU+ monocytes more so than CVD-path or SIVE.

Keywords: Galectin-3; Galectin-9; HIV-associated comorbidities; IL-18; monocyte turnover; monocyte/macrophage activation.

MeSH terms

  • Animals
  • Antigens, CD / blood
  • Antigens, Differentiation, Myelomonocytic / blood
  • Biomarkers* / blood
  • Blood Proteins / metabolism
  • Cardiovascular Diseases
  • Galectin 3* / blood
  • Galectins* / blood
  • Humans
  • Interleukin-18* / blood
  • Macaca mulatta
  • Macrophage Activation*
  • Macrophages / metabolism
  • Macrophages / virology
  • Male
  • Monocytes* / immunology
  • Monocytes* / metabolism
  • Receptors, Cell Surface / blood
  • Simian Acquired Immunodeficiency Syndrome* / blood
  • Simian Acquired Immunodeficiency Syndrome* / complications
  • Simian Acquired Immunodeficiency Syndrome* / immunology
  • Simian Immunodeficiency Virus

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • Biomarkers
  • Blood Proteins
  • CD163 antigen
  • Galectin 3
  • Galectins
  • Interleukin-18
  • LGALS3 protein, human
  • LGALS9 protein, human
  • Receptors, Cell Surface
  • IL18 protein, human