Altered mitochondrial mass and fatty acid uptake by natural killer cells in HIV-exposed uninfected children at 6 years of age.

Background: Cell metabolism is critical for adequate responses by immune cells. Although changes in immune cell populations in uninfected children born to women living with HIV (HEU children) are well described, little is known regarding the metabolic characteristics of their immune cells.

Methods: Peripheral blood mononuclear cells of 110 children at approximately 6 years of age were analysed with flow cytometry to characterize natural killer (NK) cells and measure fatty acid uptake (BODIPY FL C 16 ) and mitochondrial mass [MitoTracker Green (MTG)]. HEU children born to women initiating antiretroviral therapy (ART) during pregnancy [medium-term ART exposure (HEUMT)] ( N  = 30), before conception [long-term ART exposure (HEULT)] ( N  = 39), and 41 HIV-unexposed uninfected (HUU) children were included.

Results: Overall, NK cell frequencies were similar between HEU and HUU children. However, NKG2A +/- CD56 dim NK cells in HEUMT children had a lower fatty acid (FA) uptake compared to HEULT and HUU children. NKG2A + CD57 - CD56 dim NK cells in HEULT children had a significantly higher mitochondrial mass compared to HEUMT and HUU children. Granzyme B and perforin negatively correlated with mean fluorescence intensity (MFI) MTG in NKG2A +/- CD56 dim NK cells in HEU and HUU children, but positively correlated with MFI BODIPY FL C 16 , in HEULT children, indicating that increased mitochondrial mass and lower FA acid uptake is associated with a lower cytotoxic potential.

Conclusion: Taken together, mitochondrial mass and FA uptake differ between HEU and HUU children at 6 years of age suggesting long-term metabolic changes in HEU children. Further studies are needed to assess whether these have implications for immune competence in HEU children.