Dual RNA-Seq of Mtb-Infected Macrophages In Vivo Reveals Ontologically Distinct Host-Pathogen Interactions

Autor: Davide Pisu, Lu Huang, Jennifer K. Grenier, David G. Russell
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Cell Reports, Vol 30, Iss 2, Pp 335-350.e4 (2020)
Druh dokumentu: article
ISSN: 2211-1247
DOI: 10.1016/j.celrep.2019.12.033
Popis: Summary: 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. : In this study Pisu et al. performed dual RNA-seq on Mycobacterium tuberculosis-infected, ontogenetically distinct macrophage lineages isolated directly from infected murine lungs. The transcriptional response of host and bacteria diverged between alveolar macrophages that sustain Mtb growth and interstitial macrophages that restrict Mtb growth. Keywords: dual RNA-seq, Mycobacterium tuberculosis, tuberculosis, macrophage, alveolar macrophage, interstitial macrophage, nutritional immunity
Databáze: Directory of Open Access Journals