T cell signatures of bacterial control among M. tuberculosis 'resisters'
DownloadMeng Sun*, Jolie M. Phan*, Nathan S. Kieswetter, Krystle K.Q. Yu, Malisa T. Smith, Huang Huang, Sanjana Gupta, Gerlinde Obermoser, Holden Terry Maecker, Akshaya Krishnan, Neha Gupta, Mary Rieck, Peter Acs, Mustafa Ghanizada, Shin-Heng Chiou, Purvesh Khatri, W. Henry Boom, Thomas R. Hawn, Catherine M. Stein, Harriet Mayanja-Kizza, Mark M. Davis*, Chetan Seshadri*
Abstract: A subset of individuals with a high probability of exposure to M. tuberculosis (M.tb) appears to ‘resist’ infection, as demonstrated by serially negative tuberculin skin test (TST) or IFN-γ release assay (IGRA) results. Though ‘resisters’ (RSTR) display IFN-γ-independent T cell responses to the M.tb-specific antigens ESAT-6 and CFP-10, it is currently unknown whether specific T cell functional programs are associated with ‘resistance’ to M.tb infection. We used multi-modal single-cell RNA and TCR sequencing to compare the phenotypes and functions of ESAT-6 and CFP-10 (M.tb) specific T cells between RSTRs and matched controls with ‘latent’ TB infection (LTBI). M.tb-specific T cells were clonally expanded in both RSTRs and LTBIs, confirming the priming of adaptive immune responses after M.tb exposure. However, M.tb-specific T cells derived from RSTRs showed an early differentiation phenotype as well as enrichment of Th17-like functional programs compared to LTBIs, which were characterized by Th1-like effector phenotypes. These results were internally validated in an independent set of RSTRs and LTBIs using flow cytometry and multiplex cytokine analysis and externally validated in a cohort of long-term TB non-progressors. Enriched gene programs were also associated with bacterial control in a published study of non-human primates. Together, these data suggest that ‘resisters’ may have cleared M.tb after exposure and immune priming and establish a set of T cell biomarkers to facilitate further study of this important clinical phenotype.
DOI: None
Zenodo URL: None
Created at: 5th Jun 2024 at 19:29
Patient Visit - Metadata
No description specified
PAT-samples-publish2023-05-17_13-17.xlsx
Batch sample publishing
- samples-publish2023-05-17_13-17.xlsx
PAV-samples-publish2023-05-17_13-27.xlsx
Batch sample publishing
- samples-publish2023-05-17_13-27.xlsx
PAT-samples-publish-2024-05-21_13-17.xlsx
No description specified
- samples-publish-2024-05-21_13-17.xlsx
PAV-samples-publish-2024-05-21_13-27.xlsx
No description specified
- samples-publish-2024-05-21_13-27.xlsx
Tissue Collection - Metadata
No description specified
TIS-samples-publish2023-05-17_15-05.xlsx
Batch sample publishing
- samples-publish2023-05-17_15-05.xlsx
PAV-samples-publish2023-05-17_13-27.xlsx
Batch sample publishing
- samples-publish2023-05-17_13-27.xlsx
PAV-samples-publish-2024-05-21_13-27.xlsx
No description specified
- samples-publish-2024-05-21_13-27.xlsx
TIS-samples-publish-2024-05-21_15-05.xlsx
No description specified
- samples-publish-2024-05-21_15-05.xlsx
Flow Cytometry - Data Linked
No description specified
TIS-samples-publish2023-05-17_15-05.xlsx
Batch sample publishing
- samples-publish2023-05-17_15-05.xlsx
AB-samples-publish2023-05-17_15-29.xlsx
Batch sample publishing
- samples-publish2023-05-17_15-29.xlsx
ABP-samples-publish2023-05-17_15-30.xlsx
Batch sample publishing
- samples-publish2023-05-17_15-30.xlsx
D.FLOW-samples-publish2023-06-01_11-32.xlsx
Batch sample publishing
- samples-publish2023-06-01_11-32.xlsx
D.FCS-samples-publish2023-06-01_12-52.xlsx
Batch sample publishing
- samples-publish2023-06-01_12-52.xlsx
ABP-samples-publish-2024-05-21_15-30.xlsx
No description specified
- samples-publish-2024-05-21_15-30.xlsx
D.FCS-samples-publish-2024-05-21_12-52.xlsx
No description specified
- samples-publish-2024-05-21_12-52.xlsx
TIS-samples-publish-2024-05-21_15-05.xlsx
No description specified
- samples-publish-2024-05-21_15-05.xlsx
D.FLOW-samples-publish-2024-05-21_11-32.xlsx
No description specified
- samples-publish-2024-05-21_11-32.xlsx
AB-samples-publish-2024-05-21_15-29.xlsx
No description specified
- samples-publish-2024-05-21_15-29.xlsx
Flow Cytometry Analysis - Data Linked
No description specified
A.FLOW-samples-publish2023-05-17_15-39.xlsx
Batch sample publishing
- samples-publish2023-05-17_15-39.xlsx
D.FLOW-samples-publish2023-06-01_11-32.xlsx
Batch sample publishing
- samples-publish2023-06-01_11-32.xlsx
D.FLOW-samples-publish-2024-05-21_11-32.xlsx
No description specified
- samples-publish-2024-05-21_11-32.xlsx
All Metadata
No description specified
These checksums allow you to check a Snapshot you have downloaded hasn't been modified. For details on how to use these please visit this guide
MD5: 4e65537569a8504512540b7042968668
SHA1: 4af6bd12f7ee624480aac4652b541970a354d52a
Views: 97 Downloads: 8
Created: 5th Jun 2024 at 19:29
