Single cell analysis of M. tuberculosis phenotype and macrophage lineages in the infected lung.
Davide PisuLu HuangVipin NarangMonique TheriaultGabrielle Lê-BuryBernett LeeAgnes E LakudzalaDavid T MzinzaDavid V MhangoSteven C Mitini-NkhomaKondwani C JamboAmit SinghalHenry C MwandumbaDavid G RussellPublished in: The Journal of experimental medicine (2021)
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.
Keyphrases
- single cell
- rna seq
- high throughput
- infectious diseases
- mycobacterium tuberculosis
- genetic diversity
- adipose tissue
- escherichia coli
- physical activity
- pulmonary tuberculosis
- transcription factor
- body composition
- hiv aids
- crispr cas
- cell therapy
- stem cells
- quantum dots
- emergency department
- bone marrow
- insulin resistance
- human immunodeficiency virus
- human health
- high fat diet induced
- peripheral blood
- drug induced
- hiv infected