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| Status |
Public on Apr 20, 2024 |
| Title |
How Mycobacterium tuberculosis builds a home: Single-cell analysis reveals M. tuberculosis ESX-1-mediated accumulation of anti-inflammatory macrophages in infected mouse lungs |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Mycobacterium tuberculosis (MTB) infects and replicates in lung mononuclear phagocytes (MNPs) with astounding ability to evade elimination. A virulence determinant that contributes to MTB’s ability to survive within MNPs is ESX-1, a type VII secretion system. However, how MTB virulence factors influence mononuclear cell recruitment and/or differentiation remains unknown. Here, using single-cell RNA sequencing, we studied the role of ESX-1 in MNP heterogenicity and response in mice and murine bone marrow-derived macrophages. We found that ESX-1 is required for MTB to recruit diverse MNP subsets with high MTB burden. Further, MTB induces an anti-inflammatory signature that may lead to more permissive MNPs. Spatial transcriptomics revealed an upregulation of anti-inflammatory signals in MTB lesions, where monocyte-derived macrophages concentrate near MTB-infected cells. Together, our findings suggest that MTB ESX-1 mediates the recruitment and differentiation of anti-inflammatory MNPs, which MTB can infect and manipulate for survival.
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| Overall design |
Single cell suspension from harvested lungs from C57BL/6 uninfected or infected with H37Rv-mCherry for 28 days were stained and sorted to obtain live tissue CD45+ infected cells and bystander (mCherry negative)/uninfected cells - these were processed with manufacturer's protocol for 10X single cell library preparation.
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| Web link |
https://doi.org/10.1101/2024.04.20.590421
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| Contributor(s) |
Zha SB, Zheng W, Dorman L, Borja M, Neff N, Pisco A |
| Citation missing |
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| BioProject |
PRJNA1093473 |
| |
| Submission date |
Apr 12, 2024 |
| Last update date |
Apr 30, 2024 |
| Contact name |
Leah Dorman |
| Organization name |
CZBiohub
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| Department |
Data Science
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| Street address |
499 Illinois St
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| City |
San Francisco |
| State/province |
CA |
| ZIP/Postal code |
94158 |
| Country |
USA |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (3) |
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| This SubSeries is part of SuperSeries: |
| GSE263892 |
How Mycobacterium tuberculosis builds a home: Single-cell analysis reveals M. tuberculosis ESX-1-mediated accumulation of anti-inflammatory macrophages in infected mouse lungs |
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