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

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 human

SUBMITTER: Pisu D 

PROVIDER: S-EPMC8302446 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature