A Reproducibility-Based Computational Framework Identifies An Inducible, Enhanced Antiviral Dendritic Cell State In HIV-1 Elite Controllers (Sorted Bulk RNA-Seq). A Reproducibility-Based Computational Framework Identifies An Inducible, Enhanced Antiviral Dendritic Cell State In HIV-1 Elite Controllers (Sorted Bulk RNA-Seq)

Human immunity relies on the coordinated responses of many cellular subsets and functional states. Inter-individual variations in cellular composition and communication could thus potentially alter host protection. Here, we explore this hypothesis by applying single-cell RNA-Seq to examine viral responses among the dendritic cells (DCs) of three elite controllers (ECs) of HIV-1 infection. We discover a highly functional antiviral DC state in ECs whose fractional abundance after in vitro exposure to HIV-1 correlates with higher CD4+ T cell counts and lower HIV-1 viral loads, and that effectively primes polyfunctional T cell responses in vitro. We identify and validate select immunomodulators that increase the fractional abundance of this state in primary peripheral blood mononuclear cells (PBMCs) from healthy individuals in vitro. Overall design: Bulk RNA-seq profiling of sorted cDC subsets associated with cell-intrinsic HIV-1 immune recognition.

人类免疫系统依赖于多种细胞亚群与功能状态的协同应答。细胞组成及细胞间通讯的个体差异，或可改变宿主的免疫保护效能。本研究围绕该假说展开探索：我们采用单细胞RNA测序（single-cell RNA-Seq）技术，对3名HIV-1感染精英控制者（elite controllers, ECs）的树突状细胞（dendritic cells, DCs）进行病毒应答相关分析。我们在ECs中发现了一种功能极强的抗病毒DC状态：该状态的细胞比例在体外暴露于HIV-1后，与更高的CD4+ T细胞计数及更低的HIV-1病毒载量呈显著相关，且可在体外有效诱导多功能T细胞应答。我们筛选并验证了数种免疫调节剂，这类调节剂可在体外提升健康个体原代外周血单个核细胞（peripheral blood mononuclear cells, PBMCs）中该DC状态的细胞占比。研究整体设计：对与细胞固有HIV-1免疫识别相关的分选常规树突状细胞（conventional dendritic cell, cDC）亚群开展批量RNA测序（Bulk RNA-seq）表达谱分析。