Pisu, Davide, Huang, Lu, Narang, Vipin, Theriault, Monique, Le-Bury, Gabrielle, Lee, Bernett, Lakudzala, Agnes E, Mzinza, David T, Mhango, David V, Mitini-Nkhoma, Steven C et al (show 4 more authors)
(2021)
Single cell analysis of M. tuberculosis phenotype and macrophage lineages in the infected lung.
JOURNAL OF EXPERIMENTAL MEDICINE, 218 (9).
e20210615-.
Abstract
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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Lung, Macrophages, Alveolar, Bronchoalveolar Lavage Fluid, Animals, Mice, Inbred C57BL, Humans, Mice, Mycobacterium tuberculosis, Tuberculosis, Pulmonary, Heme, Antitubercular Agents, Sequence Analysis, RNA, Epigenesis, Genetic, Gene Expression Regulation, Bacterial, Host-Pathogen Interactions, Single-Cell Analysis, Microorganisms, Genetically-Modified, CD11 Antigens |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Infection, Veterinary and Ecological Sciences |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 14 Oct 2022 08:27 |
| Last Modified: | 08 Mar 2024 07:58 |
| DOI: | 10.1084/jem.20210615 |
| Open Access URL: | https://doi.org/10.1084/jem.20210615 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3165456 |
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