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| Status |
Public on Dec 23, 2020 |
| Title |
Defining the tuberculosis lung landscape during disease and latency using single cell technologies |
| Organism |
Macaca mulatta |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Tuberculosis (TB), caused by the bacterium Mycobacterium tuberculosis (Mtb), infects approximately one-fourth of the world’s population. The majority of infected persons are asymptomatic, but latent TB infection (LTBI) can progress to active clinical disease in 5-10% of infected individuals. The immune mechanisms that govern progression from latent to active pulmonary TB (PTB) remain poorly defined. An in-depth understanding of immune factors correlating with TB disease, as well as protection during TB, is necessary for developing new immunotherapies to promote immune control of Mtb. Experimentally Mtb-infected non-human primates (NHP) mirror the disease progression and pathology observed in humans and can recapitulate both PTB and LTBI. In the present study, we have characterized the lung immune landscape in NHPs with LTBI and PTB using high-throughput technologies including single-cell RNA sequencing (scRNA-seq) and Time of flight cytometry (CyTOF). We show that the three defining features of PTB in macaque lungs are the influx of plasmacytoid DCs (pDCs), an Interferon (IFN)-exhibiting alveolar macrophage population and predominant activated T cell responses. These features contribute to uncontrolled inflammation and disease without mediating Mtb control. In contrast, a CD27+ Natural killer (NK) cell subset accumulated in the lungs of LTBI macaques and in circulation in individuals with LTBI, thus providing novel insights into the protective lung landscape that functions during TB latency. A comprehensive understanding of the lung immune landscape as described here will improve our overall understanding of TB disease immunopathogenesis and provide novel targets for design of new therapies and vaccines for TB control.
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| Overall design |
To delineate the lung landscape at a high resolution at the single cell level, we performed 10X scRNA-seq on dematricized single cells that underwent CD45+ enrichment from the lungs of uninfected (control, n=3), PTB (n=5) and LTBI (n=3) macaques.
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| Contributor(s) |
Esaulova E, Das S, Singh DK, Choreño-Parra JA, Swain A, Arthur L, Rangel-Moreno J, Ahmed M, Bucsan A, Moodley C, Mehra S, García-Latorre E, Zuniga J, Atkinson J, Kaushal D, Artyomov MN, Khader SA |
| Citation(s) |
33340449 |
| Submission date |
May 02, 2020 |
| Last update date |
Feb 25, 2021 |
| Contact name |
Maxim N. Artyomov |
| E-mail(s) |
martyomov@pathology.wustl.edu
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| Organization name |
Washington University in St.Louis
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| Department |
Immunology&Pathology
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| Street address |
660 S. Euclid Avenue, Campus Box 8118
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| City |
St.Louis |
| State/province |
MO |
| ZIP/Postal code |
63110 |
| Country |
USA |
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| Platforms (1) |
| GPL27943 |
Illumina NovaSeq 6000 (Macaca mulatta) |
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| Samples (11)
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| Relations |
| BioProject |
PRJNA629983 |
| SRA |
SRP259962 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE149758_CD45_expData.Rda.gz |
161.8 Mb |
(ftp)(http) |
RDA |
| GSE149758_CD45_meta_data.txt.gz |
1.2 Mb |
(ftp)(http) |
TXT |
| GSE149758_RAW.tar |
132.2 Mb |
(http)(custom) |
TAR (of H5) |
| GSE149758_lymphoid_expData.Rda.gz |
32.6 Mb |
(ftp)(http) |
RDA |
| GSE149758_lymphoid_meta_data.txt.gz |
494.2 Kb |
(ftp)(http) |
TXT |
| GSE149758_myeloid_expData.Rda.gz |
118.6 Mb |
(ftp)(http) |
RDA |
| GSE149758_myeloid_meta_data.txt.gz |
951.5 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
| Processed data are available on Series record |
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