Systemic immune dysregulation in severe tuberculosis patients revealed by a single-cell transcriptome atlas.

Wang, Y; Sun, Q; Zhang, Y; Li, X; Liang, Q; Guo, R; Zhang, L; Han, X; Wang, J; Shao, L; Xue, Y; Yang, Y; Li, H; Nie, L; Shi, W; Liu, Q; Zhang, J; Duan, H; Huang, H; Luu, LDW; Tai, J; Yang, X; Wang, G

Systemic immune dysregulation in severe tuberculosis patients revealed by a single-cell transcriptome atlas.

Wang, Y Sun, Q Zhang, Y Li, X Liang, Q Guo, R Zhang, L Han, X Wang, J Shao, L Xue, Y Yang, Y Li, H Nie, L Shi, W Liu, Q Zhang, J Duan, H Huang, H Luu, LDW Tai, J Yang, X Wang, G

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Publisher:: W B SAUNDERS CO LTD
Publication Type:: Journal Article
Citation:: J Infect, 2023, 86, (5), pp. 421-438
Issue Date:: 2023-05

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Field	Value	Language
dc.contributor.author	Wang, Y
dc.contributor.author	Sun, Q
dc.contributor.author	Zhang, Y
dc.contributor.author	Li, X
dc.contributor.author	Liang, Q
dc.contributor.author	Guo, R
dc.contributor.author	Zhang, L
dc.contributor.author	Han, X
dc.contributor.author	Wang, J
dc.contributor.author	Shao, L
dc.contributor.author	Xue, Y
dc.contributor.author	Yang, Y
dc.contributor.author	Li, H
dc.contributor.author	Nie, L
dc.contributor.author	Shi, W
dc.contributor.author	Liu, Q
dc.contributor.author	Zhang, J
dc.contributor.author	Duan, H
dc.contributor.author	Huang, H
dc.contributor.author	Luu, LDW
dc.contributor.author	Tai, J
dc.contributor.author	Yang, X
dc.contributor.author	Wang, G
dc.date.accessioned	2024-02-07T07:17:44Z
dc.date.available	2023-03-28
dc.date.available	2024-02-07T07:17:44Z
dc.date.issued	2023-05
dc.identifier.citation	J Infect, 2023, 86, (5), pp. 421-438
dc.identifier.issn	0163-4453
dc.identifier.issn	1532-2742
dc.identifier.uri	http://hdl.handle.net/10453/175436
dc.description.abstract	Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb) infection, is currently the deadliest infectious disease in human that can evolve to severe forms. A comprehensive immune landscape for Mtb infection is critical for achieving TB cure, especially for severe TB patients. We performed single-cell RNA transcriptome and T-cell/B-cell receptor (TCR/BCR) sequencing of 213,358 cells from 27 samples, including 6 healthy donors and 21 active TB patients with varying severity (6 mild, 6 moderate and 9 severe cases). Two published profiles of latent TB infection were integrated for the analysis. We observed an obviously elevated proportion of inflammatory immune cells (e.g., monocytes), as well as a markedly decreased abundance of various lymphocytes (e.g., NK and γδT cells) in severe patients, revealing that lymphopenia might be a prominent feature of severe disease. Further analyses indicated that significant activation of cell apoptosis pathways, including perforin/granzyme-, TNF-, FAS- and XAF1-induced apoptosis, as well as cell migration pathways might confer this reduction. The immune landscape in severe patients was characterized by widespread immune exhaustion in Th1, CD8+T and NK cells as well as high cytotoxic state in CD8+T and NK cells. We also discovered that myeloid cells in severe TB patients may involve in the immune paralysis. Systemic upregulation of S100A12 and TNFSF13B, mainly by monocytes in the peripheral blood, may contribute to the inflammatory cytokine storms in severe patients. Our data offered a rich resource for understanding of TB immunopathogenesis and designing effective therapeutic strategies for TB, especially for severe patients.
dc.format	Print-Electronic
dc.language	eng
dc.publisher	W B SAUNDERS CO LTD
dc.relation.ispartof	J Infect
dc.relation.isbasedon	10.1016/j.jinf.2023.03.020
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	1103 Clinical Sciences
dc.subject.classification	Microbiology
dc.subject.classification	3202 Clinical sciences
dc.subject.mesh	Humans
dc.subject.mesh	Transcriptome
dc.subject.mesh	Tuberculosis
dc.subject.mesh	Mycobacterium tuberculosis
dc.subject.mesh	Latent Tuberculosis
dc.subject.mesh	Killer Cells, Natural
dc.subject.mesh	Killer Cells, Natural
dc.subject.mesh	Humans
dc.subject.mesh	Mycobacterium tuberculosis
dc.subject.mesh	Tuberculosis
dc.subject.mesh	Latent Tuberculosis
dc.subject.mesh	Transcriptome
dc.subject.mesh	Humans
dc.subject.mesh	Transcriptome
dc.subject.mesh	Tuberculosis
dc.subject.mesh	Mycobacterium tuberculosis
dc.subject.mesh	Latent Tuberculosis
dc.subject.mesh	Killer Cells, Natural
dc.title	Systemic immune dysregulation in severe tuberculosis patients revealed by a single-cell transcriptome atlas.
dc.type	Journal Article
utslib.citation.volume	86
utslib.location.activity	England
utslib.for	1103 Clinical Sciences
pubs.organisational-group	University of Technology Sydney
pubs.organisational-group	University of Technology Sydney/Faculty of Science
pubs.organisational-group	University of Technology Sydney/Faculty of Science/School of Life Sciences
utslib.copyright.status	open_access	*
dc.date.updated	2024-02-07T07:17:42Z
pubs.issue	5
pubs.publication-status	Published
pubs.volume	86
utslib.citation.issue	5

Abstract:

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb) infection, is currently the deadliest infectious disease in human that can evolve to severe forms. A comprehensive immune landscape for Mtb infection is critical for achieving TB cure, especially for severe TB patients. We performed single-cell RNA transcriptome and T-cell/B-cell receptor (TCR/BCR) sequencing of 213,358 cells from 27 samples, including 6 healthy donors and 21 active TB patients with varying severity (6 mild, 6 moderate and 9 severe cases). Two published profiles of latent TB infection were integrated for the analysis. We observed an obviously elevated proportion of inflammatory immune cells (e.g., monocytes), as well as a markedly decreased abundance of various lymphocytes (e.g., NK and γδT cells) in severe patients, revealing that lymphopenia might be a prominent feature of severe disease. Further analyses indicated that significant activation of cell apoptosis pathways, including perforin/granzyme-, TNF-, FAS- and XAF1-induced apoptosis, as well as cell migration pathways might confer this reduction. The immune landscape in severe patients was characterized by widespread immune exhaustion in Th1, CD8+T and NK cells as well as high cytotoxic state in CD8+T and NK cells. We also discovered that myeloid cells in severe TB patients may involve in the immune paralysis. Systemic upregulation of S100A12 and TNFSF13B, mainly by monocytes in the peripheral blood, may contribute to the inflammatory cytokine storms in severe patients. Our data offered a rich resource for understanding of TB immunopathogenesis and designing effective therapeutic strategies for TB, especially for severe patients.

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http://hdl.handle.net/10453/175436