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<p>Perinatally acquired HIV (PHIV) and antiretroviral therapy (ART) can alter innate immune cells, (monocytes and natural killer [NK] cells) which are important in the pathogenesis of cardiovascular disease (CVD). We compare cardiovascular biomarkers and immune signatures between adolescents with PHIV (APHIV)&#xa0;on suppressive ART and HIV-unexposed, adolescents without HIV in Uganda. Carotid intima-media thickness (IMT) is&#xa0;increased in APHIV, suggesting a higher CVD risk. Flow cytometry analysis reveals greater activation, memory, and migratory capabilities of NK cells, and increased pro-inflammatory intermediate monocytes in APHIV, and these observations are supported by transcriptomics. Many of these innate immune cell subsets are associated with carotid IMT. Plasma oxidized-LDL (Ox-LDL) is significantly lower among APHIV, and negatively correlates with pro-inflammatory, memory-like NK subsets. We demonstrate increased uptake of Ox-LDL by macrophages in the presence of activated, memory-like NK cells in vitro, suggesting a possible mechanism for greater CVD risk in APHIV. Collectively, our data demonstrate associations between dysregulated NK cell signatures and increased CVD risk among APHIV.</p>

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NK cell dysregulation may potentiate cardiovascular disease in adolescents with perinatally acquired HIV on antiretroviral therapy

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月20日

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  • Mario Alles,
  • Manuja Gunasena,
  • Aaren Kettelhut,
  • Kate Ailstock,
  • Victor Musiime,
  • Cissy Kityo,
  • Brian Richardson,
  • Will Mulhern,
  • Banumathi Tamilselvan,
  • Michael Rubsamen,
  • Ilmini De Silva,
  • Dilani Somasiri,
  • Shan Sun,
  • Grace A. McComsey,
  • Dhanuja Kasturiratna,
  • Thorsten Demberg,
  • Cheryl M. Cameron,
  • Mark J. Cameron,
  • Nicholas T. Funderburg,
  • Sahera Dirajlal-Fargo,
  • Namal P. M. Liyanage

摘要

Perinatally acquired HIV (PHIV) and antiretroviral therapy (ART) can alter innate immune cells, (monocytes and natural killer [NK] cells) which are important in the pathogenesis of cardiovascular disease (CVD). We compare cardiovascular biomarkers and immune signatures between adolescents with PHIV (APHIV) on suppressive ART and HIV-unexposed, adolescents without HIV in Uganda. Carotid intima-media thickness (IMT) is increased in APHIV, suggesting a higher CVD risk. Flow cytometry analysis reveals greater activation, memory, and migratory capabilities of NK cells, and increased pro-inflammatory intermediate monocytes in APHIV, and these observations are supported by transcriptomics. Many of these innate immune cell subsets are associated with carotid IMT. Plasma oxidized-LDL (Ox-LDL) is significantly lower among APHIV, and negatively correlates with pro-inflammatory, memory-like NK subsets. We demonstrate increased uptake of Ox-LDL by macrophages in the presence of activated, memory-like NK cells in vitro, suggesting a possible mechanism for greater CVD risk in APHIV. Collectively, our data demonstrate associations between dysregulated NK cell signatures and increased CVD risk among APHIV.