RNA-seq analysis of human monocyte derived macrophages infected with Mycobacterium tuberculosis H37Rv in the presence of extracellular acidosis

Mycobacterium tuberculosis is an intracellular pathogen of macrophages which are key to controlling infection. Inflammatory lesions infected with M. tuberculosis have an acidic extracellular microenvironment which may influence macrophage function. In this study we performed RNA-seq on primary human monocyte derived macrophages from 4 healthy donors infected with virulent M. tuberculosis H37Rv for 24 hours. Cells were infected in media at physiological pH 7.4 or acidic media pH 7.0. Appropriate uninfected control cells at pH 7.4 and pH 7.0 were also included. We were thus able to identify the principal genes and pathways regulated by M. tuberculosis infection and the influence of extracellular acidosis on these pathways. Specifically, we show that acidosis enhances transcription of matrix metalloproteinase genes and increases tissue destruction pathways in tuberculosis. RNA-seq analysis of human monocyte derived macrophages infected with Mycobacterium tuberculosis H37Rv in the presence of extracellular acidosis

结核分枝杆菌（Mycobacterium tuberculosis）是一种巨噬细胞胞内病原体，而巨噬细胞是机体控制感染的核心免疫细胞。感染结核分枝杆菌的炎性病灶存在酸性细胞外微环境，该微环境可对巨噬细胞功能产生影响。本研究针对4名健康供者来源的原代人单核细胞源性巨噬细胞开展RNA测序（RNA-seq）：将细胞以强毒力结核分枝杆菌H37Rv感染24小时，感染体系分别采用生理pH值7.4的培养基与酸性pH值7.0的培养基；同时设置了对应pH条件下的未感染对照细胞。借此，本研究得以明确结核分枝杆菌感染所调控的核心基因与通路，以及细胞外酸中毒对这些通路的调控效应。具体而言，本研究证实酸中毒可上调基质金属蛋白酶基因的转录水平，并激活结核病相关的组织破坏通路。本研究针对细胞外酸中毒环境下感染结核分枝杆菌H37Rv的人单核细胞源性巨噬细胞完成了RNA-seq分析。