Table_5_Contrasting Inflammatory Signatures in Peripheral Blood and Bronchoalveolar Cells Reveal Compartment-Specific Effects of HIV Infection.xlsx

The mechanisms by which HIV increases susceptibility to tuberculosis and other respiratory infections are incompletely understood. We used transcriptomics of paired whole bronchoalveolar lavage cells (BLCs) and peripheral blood mononuclear cells to compare the effect of HIV at the lung mucosal surface and in peripheral blood. The majority of HIV-induced differentially expressed genes (DEGs) were specific to either the peripheral or lung mucosa compartments (1,307/1,404, 93%). Type I interferon signaling was the dominant signature of DEGs in HIV-positive blood but not in HIV-positive BLCs. DEGs in the HIV-positive BLCs were significantly enriched for infiltration with cytotoxic CD8+ T cells. Higher expression of type 1 interferon transcripts in peripheral CD8+ T cells and representative transcripts and proteins in BLCs-derived CD8+ T cells during HIV infection, including IFNG (IFN-gamma), GZMB (Granzyme B), and PDCD1 (PD-1), was confirmed by cell-subset specific transcriptional analysis and flow cytometry. Thus, we report that a whole transcriptomic approach revealed qualitatively distinct effects of HIV in blood and bronchoalveolar compartments. Further work exploring the impact of distinct type I interferon programs and functional features of CD8+ T cells infiltrating the lung mucosa during HIV infection may provide novel insights into HIV-induced susceptibility to respiratory pathogens.

对于人类免疫缺陷病毒（HIV）如何增强结核病及其他呼吸道感染易感性的机制尚不完善。本研究通过对比分析配对的全肺泡灌洗细胞（BLCs）和周围血单核细胞中的转录组学数据，探讨了HIV在肺粘膜表面和周围血液中的影响。在HIV诱导的差异表达基因（DEGs）中，大多数（1,307/1,404，占比93%）具有针对周围或肺粘膜特定区域的特点。在HIV阳性的血液中，I型干扰素信号通路是DEGs的主要特征，而在HIV阳性的BLCs中则不是。在HIV阳性的BLCs中，DEGs显著富集了细胞毒性CD8+ T细胞的浸润。通过对周围CD8+ T细胞的I型干扰素转录本、BLCs衍生的CD8+ T细胞中的代表性转录本和蛋白质（包括IFNG（干扰素-γ）、GZMB（颗粒酶B）和PDCD1（程序性死亡蛋白1））的高表达进行细胞亚群特异性转录分析和流式细胞术检测，证实了上述现象。因此，我们报告了一种全转录组学方法揭示了HIV在血液和支气管肺泡区域中作用的质区别。进一步研究不同I型干扰素程序和CD8+ T细胞在HIV感染期间浸润肺粘膜的功能特性，可能会为HIV引发的呼吸道病原体易感性提供新的见解。