CD160 Promotes NK Cell Functions by Upregulating Glucose Metabolism and Negatively Correlates With HIV Disease Progression

Front Immunol. 2022 Aug 19:13:854432. doi: 10.3389/fimmu.2022.854432. eCollection 2022.

Abstract

Natural killer (NK) cells are crucial for immune responses to viral infections. CD160 is an important NK cell activating receptor, with unknown function in HIV infection. Here, we found that CD160 expression was reduced on NK cells from HIV-infected individuals and its expression was negatively correlated with HIV disease progression. Further, GLUT1 expression and glucose uptake were higher in CD160+ NK cells, and the results of RNA-seq and flow cytometry demonstrated that CD160 positively regulated glucose metabolism through the PI3K/AKT/mTOR/s6k signaling pathway, thereby enhancing NK cell function. Moreover, we determined that reduced CD160 expression on NK cells could be attributed to the higher plasma levels of TGF-β1 in HIV-infected individuals. Overall, these results highlight the vital role of CD160 in HIV disease progression and regulation of glucose metabolism, indicating a potential target for HIV immunotherapy.

Keywords: CD160; HIV; NK cells; PI3K/AKT/mTOR/s6k signaling pathway; TGF-β1; glucose metabolism.

MeSH terms

  • Antigens, CD* / metabolism
  • Disease Progression
  • GPI-Linked Proteins / metabolism
  • Glucose / metabolism
  • Glucose Transporter Type 1 / metabolism
  • HIV Infections*
  • Humans
  • Killer Cells, Natural
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Receptors, Immunologic / metabolism
  • TOR Serine-Threonine Kinases / metabolism
  • Transforming Growth Factor beta1 / metabolism

Substances

  • Antigens, CD
  • CD160 protein, human
  • GPI-Linked Proteins
  • Glucose Transporter Type 1
  • Receptors, Immunologic
  • Transforming Growth Factor beta1
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases
  • Glucose