IL-15-dependent immune crosstalk between natural killer cells and dendritic cells in HIV-1 elite controllers.
IL-15-dependent immune crosstalk between natural killer cells and dendritic cells in HIV-1 elite controllers.
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DOI：
10.1016/j.celrep.2023.113530
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发表时间：
2023-12-26
期刊：
影响因子：
8.8
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中科院分区：
文献类型：
--
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作为先天免疫系统的主要效应细胞群，自然杀伤（NK）细胞可能在自然免疫介导的HIV-1复制控制中发挥重要作用。通过对激活和抑制染色质特征的全基因组评估，我们在这里证明了来自精英控制者（ECs）的细胞毒性NK （cNK）细胞在白细胞介素2 (IL-2)/IL-15受体β链和BCL2基因位点上显示了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的反应性增加，这与ec中髓样树突状细胞更高水平的IL-15转录相一致。这些先天免疫细胞群之间独特的免疫串音导致il -15依赖性cNK细胞存活和细胞毒性的改善，并与il -15介导的糖酵解活性的代谢谱相匹配。总之，这些结果表明，来自ECs的cNK细胞显示出程序化的IL-15应答信号，并支持先天免疫途径在自然、无药物控制HIV-1中的新作用。IL-15刺激后ECs cNK细胞的糖溶酶活性增加Hartana等人观察到来自HIV-1精英控制者的cNK细胞对IL-15的反应性升高，同时mDCs中IL-15转录水平升高。这些结果表明，mDCs和cNK细胞之间的免疫串扰导致不同的IL-15应答信号，并可能有助于无药物控制HIV-1复制。
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. Enhanced activating histone marks on IL2Rβ and BCL2 genes in cNK cells from ECs Elevated levels of IL-15 transcription in myeloid DCs from ECs Improved survival and increased cytotoxicity in cNK cells after IL-15 stimulation Increased glycolytic activities in cNK cells from ECs after IL-15 stimulation Hartana et al. observed elevated IL-15 responsiveness of cNK cells from HIV-1 elite controllers, paired with increased levels of IL-15 transcription in mDCs. These results suggest that immune crosstalk between mDCs and cNK cells results in distinct IL-15 response signatures and may contribute to drug-free control of HIV-1 replication.
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影响因子：
17.1
作者：
Horowitz A;Strauss-Albee DM;Leipold M;Kubo J;Nemat-Gorgani N;Dogan OC;Dekker CL;Mackey S;Maecker H;Swan GE;Davis MM;Norman PJ;Guethlein LA;Desai M;Parham P;Blish CA
通讯作者：
Blish CA
影响因子：
4.6
作者：
Diez-Fuertes, Francisco;Erick De La Torre-Tarazona, Humberto;Alcami, Jose
通讯作者：
Alcami, Jose
影响因子：
7.3
作者：
Fisher, Leigh;Zinter, Melissa;Ferrari, Guido
通讯作者：
Ferrari, Guido
影响因子：
4.1
作者：
Hartana CA;Yu XG
通讯作者：
Yu XG
影响因子：
64.5
作者：
Hsu, Jingmei;Van Besien, Koen;Bryson, Yvonne
通讯作者：
Bryson, Yvonne