PDF(Pubmed)
Abstract：
As the principal effector cell population of the innate immune system, natural killer (NK) cells may make critical contributions to natural, immune-mediated control of HIV-1 replication. Using genome-wide assessments of activating and inhibitory chromatin features, we demonstrate here that cytotoxic NK (cNK) cells from elite controllers (ECs) display elevated activating histone modifications at the interleukin 2 (IL-2)/IL-15 receptor β chain and the BCL2 gene loci. These histone changes translate into increased responsiveness of cNK cells to paracrine IL-15 secretion, which coincides with higher levels of IL-15 transcription by myeloid dendritic cells in ECs. The distinct immune crosstalk between these innate immune cell populations results in improved IL-15-dependent cNK cell survival and cytotoxicity, paired with a metabolic profile biased toward IL-15-mediated glycolytic activities. Together, these results suggest that cNK cells from ECs display a programmed IL-15 response signature and support the emerging role of innate immune pathways in natural, drug-free control of HIV-1.
摘要：
作为先天免疫系统的主要效应细胞群体，自然杀伤（NK）细胞可能对自然，免疫介导的HIV-1复制控制。使用激活和抑制染色质特征的全基因组评估，我们在此证明，来自精英控制者（EC）的细胞毒性NK（cNK）细胞在白介素2（IL-2）/IL-15受体β链和BCL2基因位点显示出升高的激活组蛋白修饰。这些组蛋白变化转化为cNK细胞对旁分泌IL-15分泌的反应性增加，这与ECs中髓样树突状细胞的IL-15转录水平更高一致。这些先天免疫细胞群体之间的独特免疫串扰导致改善的IL-15依赖性cNK细胞存活和细胞毒性。与偏向IL-15介导的糖酵解活性的代谢谱配对。一起,这些结果表明，来自ECs的cNK细胞显示出程序化的IL-15反应特征，并支持天然免疫途径在自然，HIV-1的无毒品控制。
