1. Single cell analysis of M. tuberculosis phenotype and macrophage lineages in the infected lung
- Author
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Kondwani C. Jambo, Davide Pisu, David Mzinza, Gabrielle Lê-Bury, Monique E. Theriault, David V Mhango, Amit Singhal, Lu Huang, Steven C. Mitini-Nkhoma, Agnes E Lakudzala, Bernett Lee, Vipin Narang, David G. Russell, and Henry C. Mwandumba
- Subjects
0301 basic medicine ,Immunology ,genetic processes ,Antitubercular Agents ,Heme ,Biology ,Technical Advances and Resources ,Microbiology ,Epigenesis, Genetic ,Transcriptome ,Infectious Disease and Host Defense ,03 medical and health sciences ,0302 clinical medicine ,qu_58.7 ,Single-cell analysis ,In vivo ,Macrophages, Alveolar ,Immunology and Allergy ,Macrophage ,Animals ,Humans ,natural sciences ,Lung ,Tuberculosis, Pulmonary ,wh_650 ,Innate immune system ,CD11 Antigens ,Sequence Analysis, RNA ,Mucosal Immunology ,Gene Expression Regulation, Bacterial ,Mycobacterium tuberculosis ,respiratory system ,biology.organism_classification ,Phenotype ,respiratory tract diseases ,Mice, Inbred C57BL ,030104 developmental biology ,Metabolism ,Infectious disease (medical specialty) ,030220 oncology & carcinogenesis ,Host-Pathogen Interactions ,wf_200 ,Microorganisms, Genetically-Modified ,Single-Cell Analysis ,Bronchoalveolar Lavage Fluid ,Bacteria - Abstract
Through scRNA-seq and ATAC-seq, Pisu et al. characterize specific lung macrophage subsets that either restrict or promote M. tuberculosis growth. Comparable macrophage populations are present in the human airways, and cells show evidence of epigenetic imprinting., 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., Graphical Abstract
- Published
- 2021