Lyu, M. et al. (2024) Single-cell sequencing reveals functional alterations in tuberculosis. Advanced Science, (doi: 10.1002/advs.202305592) (PMID:38192178) (Early Online Publication)
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Abstract
Despite its importance, the functional heterogeneity surrounding the dynamics of interactions between mycobacterium tuberculosis and human immune cells in determining host immune strength and tuberculosis (TB) outcomes, remains far from understood. This work now describes the development of a new technological platform to elucidate the immune function differences in individuals with TB, integrating single-cell RNA sequencing and cell surface antibody sequencing to provide both genomic and phenotypic information from the same samples. Single-cell analysis of 23 990 peripheral blood mononuclear cells from a new cohort of primary TB patients and healthy controls enables to not only show four distinct immune phenotypes (TB, myeloid, and natural killer (NK) cells), but also determine the dynamic changes in cell population abundance, gene expression, developmental trajectory, transcriptomic regulation, and cell–cell signaling. In doing so, TB-related changes in immune cell functions demonstrate that the immune response is mediated through host T cells, myeloid cells, and NK cells, with TB patients showing decreased naive, cytotoxicity, and memory functions of T cells, rather than their immunoregulatory function. The platform also has the potential to identify new targets for immunotherapeutic treatment strategies to restore T cells from dysfunctional or exhausted states.
| Item Type: | Articles |
|---|---|
| Additional Information: | This work was supported by the National Natural Science Foundation of China [Grant numbers: 82272416, 82302624 and 82102968], the China Postdoctoral Science Foundation [Grant numbers: 2023M732451 and 2023T160452], the Post-Doctor Research Project of West China Hospital Sichuan University [Grant numbers: 2023HXBH069], and the United Kingdom Research and Innovation Medical Research Council (MR/V035401/1). |
| Keywords: | tuberculosis, single-cell sequencing, heterogeneity, functional variation, immunosuppression. |
| Status: | Early Online Publication |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Cooper, Professor Jonathan and Reboud, Professor Julien |
| Authors: | Lyu, M., Xu, G., Zhou, J., Reboud, J., Wang, Y., Lai, H., Chen, Y., Zhou, Y., Zhu, G., Cooper, J. M., and Ying, B. |
| College/School: | College of Science and Engineering > School of Engineering > Biomedical Engineering |
| Journal Name: | Advanced Science |
| Publisher: | Wiley |
| ISSN: | 2198-3844 |
| ISSN (Online): | 2198-3844 |
| Published Online: | 08 January 2024 |
| Copyright Holders: | Copyright © 2024 The Authors |
| First Published: | First published in Advanced Science 2024 |
| Publisher Policy: | Reproduced under a Creative Commons License |
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