Mataramvura Hope, Jordan-Paiz Ana, Naidoo Kewreshini, Jaeger Julia, Testa Lucia, Gumbo Felicity Z, Mazengera Ronald L, Bunders Madeleine J, Duri Kerina
Immunology Unit, Department of Laboratory Diagnostic and Investigative Sciences, University of Zimbabwe Faculty of Medicine and Health Sciences (UZ-FMHS), Harare, Zimbabwe.
Department of Virus Immunology, Leibniz Institute of Virology, Hamburg, Germany.
AIDS. 2025 May 3. doi: 10.1097/QAD.0000000000004228.
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.
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 measured fatty acid (FA) uptake (BODIPY FL C 16 ) and mitochondrial mass (MM) (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.
Overall, NK cell frequencies were similar between HEU and HUU children. However, NKG2A +/- CD56 dim NK cells in HEUMT children had a lower FA uptake compared to HEULT and HUU children. NKG2A + CD57 - CD56 dim NK cells in HEULT children had a significantly higher MM 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 MM and lower FA acid uptake is associated with a lower cytotoxic potential.
Taken together, MM 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.
细胞代谢对于免疫细胞做出充分反应至关重要。虽然对感染艾滋病毒的女性所生未感染儿童（艾滋病毒暴露儿童）的免疫细胞群体变化已有充分描述，但对其免疫细胞的代谢特征却知之甚少。
采用流式细胞术分析了110名约6岁儿童的外周血单个核细胞，以表征自然杀伤（NK）细胞，并测量脂肪酸（FA）摄取（BODIPY FL C 16）和线粒体质量（MM）（MitoTracker Green（MTG））。纳入了孕期开始抗逆转录病毒治疗（ART）的女性所生的艾滋病毒暴露儿童[中期ART暴露（HEUMT）]（N = 30）、受孕前[长期ART暴露（HEULT）]（N = 39）以及41名未暴露于艾滋病毒的未感染（HUU）儿童。
总体而言，艾滋病毒暴露儿童和未暴露儿童的NK细胞频率相似。然而，与长期ART暴露儿童和未暴露儿童相比，中期ART暴露儿童中NKG2A+/- CD56dim NK细胞的FA摄取较低。与中期ART暴露儿童和未暴露儿童相比，长期ART暴露儿童中NKG2A + CD57 - CD56dim NK细胞的MM显著更高。颗粒酶B和穿孔素与艾滋病毒暴露儿童和未暴露儿童中NKG2A+/- CD56dim NK细胞的平均荧光强度（MFI）MTG呈负相关，但与长期ART暴露儿童中MFI BODIPY FL C 16呈正相关，这表明MM增加和FA摄取降低与较低的细胞毒性潜力相关。
综上所述,6岁的艾滋病毒暴露儿童和未暴露儿童在MM和FA摄取方面存在差异，这表明艾滋病毒暴露儿童存在长期代谢变化。需要进一步研究来评估这些变化是否对艾滋病毒暴露儿童的免疫能力有影响。
