Single cell analysis of M. tuberculosis phenotype and macrophage lineages in the infected lung

Pisu, Davide, Huang, Lu, Narang, Vipin, Theriault, Monique, Lê-Bury, Gabrielle, Lee, Bernett, Lakudzala, Agnes E, Mzinza, David T, Mhango, David V, Mitini-Nkhoma, Steven C, Jambo, Kondwani ORCID: https://orcid.org/0000-0002-3195-2210, Singhal, Amit, Mwandumba, Henry ORCID: https://orcid.org/0000-0003-4470-3608 and Russell, David G (2021) 'Single cell analysis of M. tuberculosis phenotype and macrophage lineages in the infected lung'. The Journal of experimental medicine, Vol 218, Issue 9, e20210615.

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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
Subjects:	QU Biochemistry > Proteins. Amino Acids. Peptides > QU 58.7 RNA WF Respiratory System > Tuberculosis > WF 200 Tuberculosis (General) WH Hemic and Lymphatic Systems > Lymphatic System > WH 650 Reticuloendothelial system
Faculty: Department:	Clinical Sciences & International Health > Clinical Sciences Department Clinical Sciences & International Health > Malawi-Liverpool-Wellcome Programme (MLW)
Digital Object Identifer (DOI):	https://doi.org/10.1084/jem.20210615
Depositing User:	Julie Franco
Date Deposited:	11 Aug 2021 13:13
Last Modified:	07 Aug 2023 08:25
URI:	https://archive.lstmed.ac.uk/id/eprint/18616

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