Department of Medicine, Stanford University, Stanford, CA, USA.
Bakar Computational Health Sciences Institute, University of California, San Francisco, San Francisco, CA, USA.
Sci Transl Med. 2023 Jan 25;15(680):eadd9012. doi: 10.1126/scitranslmed.add9012.
Natural killer (NK) cells likely play an important role in immunity to malaria, but the effect of repeated malaria on NK cell responses remains unclear. Here, we comprehensively profiled the NK cell response in a cohort of 264 Ugandan children. Repeated malaria exposure was associated with expansion of an atypical, CD56 population of NK cells that differed transcriptionally, epigenetically, and phenotypically from CD56 NK cells, including decreased expression of PLZF and the Fc receptor γ-chain, increased histone methylation, and increased protein expression of LAG-3, KIR, and LILRB1. CD56 NK cells were highly functional and displayed greater antibody-dependent cellular cytotoxicity than CD56 NK cells. Higher frequencies of CD56 NK cells were associated with protection against symptomatic malaria and high parasite densities. After marked reductions in malaria transmission, frequencies of these cells rapidly declined, suggesting that continuous exposure to is required to maintain this modified, adaptive-like NK cell subset.
自然杀伤 (NK) 细胞可能在对疟疾的免疫中发挥重要作用，但反复感染疟疾对 NK 细胞反应的影响尚不清楚。在这里，我们对 264 名乌干达儿童进行了 NK 细胞反应的全面分析。反复暴露于疟疾与不典型的 CD56 NK 细胞群体的扩增有关，该群体在转录、表观遗传和表型上与 CD56 NK 细胞不同，包括 PLZF 和 Fc 受体 γ 链的表达降低、组蛋白甲基化增加以及 LAG-3、KIR 和 LILRB1 的蛋白表达增加。CD56 NK 细胞具有高度的功能，表现出比 CD56 NK 细胞更强的抗体依赖性细胞毒性。CD56 NK 细胞的频率与对有症状疟疾和高寄生虫密度的保护有关。在疟疾传播显著减少后，这些细胞的频率迅速下降，这表明需要持续接触疟疾才能维持这种改良的、适应性样 NK 细胞亚群。
