Dual RNA-Seq of Mtb-Infected Macrophages In Vivo Reveals Ontologically Distinct Host-Pathogen Interactions.
Mycobacterium tuberculosis
alveolar macrophage
dual RNA-seq
interstitial macrophage
macrophage
nutritional immunity
tuberculosis
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
14 01 2020
14 01 2020
Historique:
received:
02
07
2019
revised:
31
10
2019
accepted:
10
12
2019
entrez:
16
1
2020
pubmed:
16
1
2020
medline:
13
2
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31940480
pii: S2211-1247(19)31683-3
doi: 10.1016/j.celrep.2019.12.033
pmc: PMC7032562
mid: NIHMS1549887
pii:
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
335-350.e4Subventions
Organisme : NIAID NIH HHS
ID : R01 AI118582
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI134183
Pays : United States
Informations de copyright
Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.
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