生物
体内
细胞内
结核分枝杆菌
病菌
巨噬细胞
微生物学
细胞内寄生虫
转录组
离体
一氧化氮
细胞生物学
基因表达
肺结核
基因
体外
遗传学
病理
内分泌学
医学
作者
Davide Pisu,Lu Huang,Jennifer K. Grenier,David G. Russell
出处
期刊:Cell Reports
[Elsevier]
日期:2020-01-01
卷期号:30 (2): 335-350.e4
被引量:163
标识
DOI:10.1016/j.celrep.2019.12.033
摘要
Dissecting the in vivo host-pathogen interplay is crucial to understanding the molecular mechanisms governing control or progression of intracellular infections. In this work, we explore the in vivo molecular dynamics of Mtb infection by performing dual RNA-seq on Mycobacterium tuberculosis-infected, ontogenetically distinct macrophage lineages isolated directly from murine lungs. We first define an in vivo signature of 180 genes specifically upregulated by Mtb in mouse lung macrophages, then we uncover a divergent transcriptional response of the bacteria between alveolar macrophages that appear to sustain Mtb growth through increased access to iron and fatty acids and interstitial macrophages that restrict Mtb growth through iron sequestration and higher levels of nitric oxide. We use an enrichment protocol for bacterial transcripts, which enables us to probe Mtb physiology at the host cell level in an in vivo environment, with broader application in understanding the infection dynamics of intracellular pathogens in general.
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