Single cell analysis of M. tuberculosis phenotype and macrophage lineages in the infected lung.
Animals
Antitubercular Agents
/ pharmacology
Bronchoalveolar Lavage Fluid
/ microbiology
CD11 Antigens
/ immunology
Epigenesis, Genetic
Gene Expression Regulation, Bacterial
Heme
/ metabolism
Host-Pathogen Interactions
Humans
Lung
/ microbiology
Macrophages, Alveolar
/ immunology
Mice, Inbred C57BL
Microorganisms, Genetically-Modified
Mycobacterium tuberculosis
/ drug effects
Sequence Analysis, RNA
Single-Cell Analysis
Tuberculosis, Pulmonary
/ genetics
Journal
The Journal of experimental medicine
ISSN: 1540-9538
Titre abrégé: J Exp Med
Pays: United States
ID NLM: 2985109R
Informations de publication
Date de publication:
06 09 2021
06 09 2021
Historique:
received:
18
03
2021
revised:
19
05
2021
accepted:
24
06
2021
entrez:
22
7
2021
pubmed:
23
7
2021
medline:
25
11
2021
Statut:
ppublish
Résumé
In this study, we detail a novel approach that combines bacterial fitness fluorescent reporter strains with scRNA-seq to simultaneously acquire the host transcriptome, surface marker expression, and bacterial phenotype for each infected cell. This approach facilitates the dissection of the functional heterogeneity of M. tuberculosis-infected alveolar (AMs) and interstitial macrophages (IMs) in vivo. We identify clusters of pro-inflammatory AMs associated with stressed bacteria, in addition to three different populations of IMs with heterogeneous bacterial phenotypes. Finally, we show that the main macrophage populations in the lung are epigenetically constrained in their response to infection, while inter-species comparison reveals that most AMs subsets are conserved between mice and humans. This conceptual approach is readily transferable to other infectious disease agents with the potential for an increased understanding of the roles that different host cell populations play during the course of an infection.
Identifiants
pubmed: 34292313
pii: 212500
doi: 10.1084/jem.20210615
pmc: PMC8302446
pii:
doi:
Substances chimiques
Antitubercular Agents
0
CD11 Antigens
0
Itgax protein, mouse
0
Heme
42VZT0U6YR
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIAID NIH HHS
ID : R33 AI136097
Pays : United States
Organisme : NIH HHS
ID : R01HL152078
Pays : United States
Organisme : Medical Research Council
ID : MR/P020526/1
Pays : United Kingdom
Organisme : NHLBI NIH HHS
ID : R01 HL152078
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI134183
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI155319
Pays : United States
Organisme : NIH HHS
ID : AI134183
Pays : United States
Organisme : Bill & Melinda Gates Foundation
ID : OPP1108452
Pays : United States
Organisme : Medical Research Council
ID : MR/T008822/1
Pays : United Kingdom
Organisme : NIAID NIH HHS
ID : R21 AI136097
Pays : United States
Informations de copyright
© 2021 Pisu et al.
Déclaration de conflit d'intérêts
Disclosures: The authors declare no competing interests exist.
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