Single-cell landscape revealed immune characteristics associated with disease phases in brucellosis patients.

Wang, Y; Yang, S; Han, B; Du, X; Sun, H; Du, Y; Liu, Y; Lu, P; Di, J; Luu, LDW; Lv, X; Hu, S; Wang, L; Jiang, R

Single-cell landscape revealed immune characteristics associated with disease phases in brucellosis patients.

Wang, Y Yang, S Han, B Du, X Sun, H Du, Y Liu, Y Lu, P Di, J Luu, LDW Lv, X Hu, S Wang, L Jiang, R

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Publisher:: Wiley
Publication Type:: Journal Article
Citation:: Imeta, 2024, 3, (4), pp. e226
Issue Date:: 2024-08

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Field	Value	Language
dc.contributor.author	Wang, Y
dc.contributor.author	Yang, S
dc.contributor.author	Han, B
dc.contributor.author	Du, X
dc.contributor.author	Sun, H
dc.contributor.author	Du, Y
dc.contributor.author	Liu, Y
dc.contributor.author	Lu, P
dc.contributor.author	Di, J
dc.contributor.author	Luu, LDW
dc.contributor.author	Lv, X
dc.contributor.author	Hu, S
dc.contributor.author	Wang, L
dc.contributor.author	Jiang, R
dc.date.accessioned	2024-08-21T03:44:53Z
dc.date.available	2024-07-04
dc.date.available	2024-08-21T03:44:53Z
dc.date.issued	2024-08
dc.identifier.citation	Imeta, 2024, 3, (4), pp. e226
dc.identifier.issn	2770-5986
dc.identifier.issn	2770-596X
dc.identifier.uri	http://hdl.handle.net/10453/180444
dc.description.abstract	A comprehensive immune landscape for Brucella infection is crucial for developing new treatments for brucellosis. Here, we utilized single-cell RNA sequencing (scRNA-seq) of 290,369 cells from 35 individuals, including 29 brucellosis patients from acute (n = 10), sub-acute (n = 9), and chronic (n = 10) phases as well as six healthy donors. Enzyme-linked immunosorbent assays were applied for validation within this cohort. Brucella infection caused a significant change in the composition of peripheral immune cells and inflammation was a key feature of brucellosis. Acute patients are characterized by potential cytokine storms resulting from systemic upregulation of S100A8/A9, primarily due to classical monocytes. Cytokine storm may be mediated by activating S100A8/A9-TLR4-MyD88 signaling pathway. Moreover, monocytic myeloid-derived suppressor cells were the probable contributors to immune paralysis in acute patients. Chronic patients are characterized by a dysregulated Th1 response, marked by reduced expression of IFN-γ and Th1 signatures as well as a high exhausted state. Additionally, Brucella infection can suppress apoptosis in myeloid cells (e.g., mDCs, classical monocytes), inhibit antigen presentation in professional antigen-presenting cells (APCs; e.g., mDC) and nonprofessional APCs (e.g., monocytes), and induce exhaustion in CD8+ T/NK cells, potentially resulting in the establishment of chronic infection. Overall, our study systemically deciphered the coordinated immune responses of Brucella at different phases of the infection, which facilitated a full understanding of the immunopathogenesis of brucellosis and may aid the development of new effective therapeutic strategies, especially for those with chronic infection.
dc.format	Electronic-eCollection
dc.language	eng
dc.publisher	Wiley
dc.relation	University of Technology Sydney
dc.relation.ispartof	Imeta
dc.relation.isbasedon	10.1002/imt2.226
dc.rights	info:eu-repo/semantics/openAccess
dc.title	Single-cell landscape revealed immune characteristics associated with disease phases in brucellosis patients.
dc.type	Journal Article
utslib.citation.volume	3
utslib.location.activity	Australia
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.rights.license	This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0). To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/
dc.date.updated	2024-08-21T03:44:45Z
pubs.issue	4
pubs.publication-status	Published online
pubs.volume	3
utslib.citation.issue	4

Abstract:

A comprehensive immune landscape for Brucella infection is crucial for developing new treatments for brucellosis. Here, we utilized single-cell RNA sequencing (scRNA-seq) of 290,369 cells from 35 individuals, including 29 brucellosis patients from acute (n = 10), sub-acute (n = 9), and chronic (n = 10) phases as well as six healthy donors. Enzyme-linked immunosorbent assays were applied for validation within this cohort. Brucella infection caused a significant change in the composition of peripheral immune cells and inflammation was a key feature of brucellosis. Acute patients are characterized by potential cytokine storms resulting from systemic upregulation of S100A8/A9, primarily due to classical monocytes. Cytokine storm may be mediated by activating S100A8/A9-TLR4-MyD88 signaling pathway. Moreover, monocytic myeloid-derived suppressor cells were the probable contributors to immune paralysis in acute patients. Chronic patients are characterized by a dysregulated Th1 response, marked by reduced expression of IFN-γ and Th1 signatures as well as a high exhausted state. Additionally, Brucella infection can suppress apoptosis in myeloid cells (e.g., mDCs, classical monocytes), inhibit antigen presentation in professional antigen-presenting cells (APCs; e.g., mDC) and nonprofessional APCs (e.g., monocytes), and induce exhaustion in CD8+ T/NK cells, potentially resulting in the establishment of chronic infection. Overall, our study systemically deciphered the coordinated immune responses of Brucella at different phases of the infection, which facilitated a full understanding of the immunopathogenesis of brucellosis and may aid the development of new effective therapeutic strategies, especially for those with chronic infection.

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http://hdl.handle.net/10453/180444