Gene expression profling of BAL cells in people living with HIV and healthy controls in response to Mtb infection at single cell resolution

Understanding why PLWH remain highly susceptible to TB despite anti-retroviral therapy (ART) is critical for improving treatment and prevention strategies. We aimed to determine how HIV impacts the transcriptional responses of AMs and other immune cells in response to Mtb infection at the single cell level using ScRNAseq. Our analyses revealed that transcriptional responses of AMs from PLWH following Mtb infection show significant deficits in costimulatory capacity and TNF/IL-6 signaling networks. Overall design: Bronchoalveolar lavage (BAL) samples were collected from HC and PLWH on ART in Atlanta, GA. Single cell transcriptional profiling was assessed by scRNAseq (10x Genomics), both at baseline and after 4 hours of infection with Mtb ex vivo.

明确尽管接受抗逆转录病毒治疗（anti-retroviral therapy, ART），艾滋病病毒感染者（People Living with HIV, PLWH）仍对结核病保持高度易感性的机制，对于优化结核病的治疗与预防策略具有关键意义。本研究旨在通过单细胞RNA测序（single-cell RNA sequencing, scRNAseq）技术，在单细胞层面解析HIV如何影响肺泡巨噬细胞（alveolar macrophages, AMs）及其他免疫细胞针对结核分枝杆菌（Mycobacterium tuberculosis, Mtb）感染的转录应答反应。分析结果显示，来自PLWH的肺泡巨噬细胞在感染Mtb后，其共刺激能力以及肿瘤坏死因子/白细胞介素-6（TNF/IL-6）信号通路网络的转录应答存在显著缺陷。实验整体设计：从美国佐治亚州亚特兰大市的健康对照者（healthy control, HC）以及接受ART治疗的PLWH体内采集支气管肺泡灌洗液（bronchoalveolar lavage, BAL）样本；通过10x Genomics平台的单细胞RNA测序技术，对样本在基线状态以及体外感染Mtb 4小时后的转录组特征进行分析。