Zebrafish tsc1 and cxcl12a increase susceptibility to mycobacterial infection.

Wright, K; Han, DJ; Song, R; de Silva, K; Plain, KM; Purdie, AC; Shepherd, A; Chin, M; Hortle, E; Wong, JJ-L; Britton, WJ; Oehlers, SH

Zebrafish tsc1 and cxcl12a increase susceptibility to mycobacterial infection.

Wright, K Han, DJ Song, R de Silva, K

Plain, KM Purdie, AC Shepherd, A Chin, M Hortle, E

Wong, JJ-L Britton, WJ Oehlers, SH

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Publisher:: LIFE SCIENCE ALLIANCE LLC
Publication Type:: Journal Article
Citation:: Life Sci Alliance, 2024, 7, (4), pp. e202302523
Issue Date:: 2024-04

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Field	Value	Language
dc.contributor.author	Wright, K
dc.contributor.author	Han, DJ
dc.contributor.author	Song, R
dc.contributor.author	de Silva, K https://orcid.org/0000-0001-5973-5077
dc.contributor.author	Plain, KM
dc.contributor.author	Purdie, AC
dc.contributor.author	Shepherd, A
dc.contributor.author	Chin, M
dc.contributor.author	Hortle, E https://orcid.org/0000-0001-9633-5638
dc.contributor.author	Wong, JJ-L
dc.contributor.author	Britton, WJ
dc.contributor.author	Oehlers, SH
dc.date.accessioned	2024-08-06T03:06:16Z
dc.date.available	2024-01-23
dc.date.available	2024-08-06T03:06:16Z
dc.date.issued	2024-04
dc.identifier.citation	Life Sci Alliance, 2024, 7, (4), pp. e202302523
dc.identifier.issn	2575-1077
dc.identifier.issn	2575-1077
dc.identifier.uri	http://hdl.handle.net/10453/180083
dc.description.abstract	Regulation of host miRNA expression is a contested node that controls the host immune response to mycobacterial infection. The host must counter subversive efforts of pathogenic mycobacteria to launch a protective immune response. Here, we examine the role of miR-126 in the zebrafish-Mycobacterium marinum infection model and identify a protective role for infection-induced miR-126 through multiple effector pathways. We identified a putative link between miR-126 and the tsc1a and cxcl12a/ccl2/ccr2 signalling axes resulting in the suppression of non-tnfa expressing macrophage accumulation at early M. marinum granulomas. Mechanistically, we found a detrimental effect of tsc1a expression that renders zebrafish embryos susceptible to higher bacterial burden and increased cell death via mTOR inhibition. We found that macrophage recruitment driven by the cxcl12a/ccl2/ccr2 signalling axis was at the expense of the recruitment of classically activated tnfa-expressing macrophages and increased cell death around granulomas. Together, our results delineate putative pathways by which infection-induced miR-126 may shape an effective immune response to M. marinum infection in zebrafish embryos.
dc.format	Electronic-Print
dc.language	eng
dc.publisher	LIFE SCIENCE ALLIANCE LLC
dc.relation	http://purl.org/au-research/grants/nhmrc/1153493
dc.relation	http://purl.org/au-research/grants/nhmrc/GNT1153493
dc.relation.ispartof	Life Sci Alliance
dc.relation.isbasedon	10.26508/lsa.202302523
dc.rights	info:eu-repo/semantics/openAccess
dc.subject.classification	31 Biological sciences
dc.subject.classification	32 Biomedical and clinical sciences
dc.subject.mesh	Animals
dc.subject.mesh	Granuloma
dc.subject.mesh	Macrophages
dc.subject.mesh	MicroRNAs
dc.subject.mesh	Mycobacterium Infections, Nontuberculous
dc.subject.mesh	Zebrafish
dc.subject.mesh	Tuberous Sclerosis Complex 1 Protein
dc.subject.mesh	Chemokine CXCL12
dc.subject.mesh	Zebrafish Proteins
dc.subject.mesh	Macrophages
dc.subject.mesh	Animals
dc.subject.mesh	Zebrafish
dc.subject.mesh	Granuloma
dc.subject.mesh	Zebrafish Proteins
dc.subject.mesh	MicroRNAs
dc.subject.mesh	Chemokine CXCL12
dc.subject.mesh	Mycobacterium Infections, Nontuberculous
dc.subject.mesh	Tuberous Sclerosis Complex 1 Protein
dc.subject.mesh	Animals
dc.subject.mesh	Granuloma
dc.subject.mesh	Macrophages
dc.subject.mesh	MicroRNAs
dc.subject.mesh	Mycobacterium Infections, Nontuberculous
dc.subject.mesh	Zebrafish
dc.subject.mesh	Tuberous Sclerosis Complex 1 Protein
dc.subject.mesh	Chemokine CXCL12
dc.subject.mesh	Zebrafish Proteins
dc.title	Zebrafish tsc1 and cxcl12a increase susceptibility to mycobacterial infection.
dc.type	Journal Article
utslib.citation.volume	7
utslib.location.activity	United States
pubs.organisational-group	University of Technology Sydney
pubs.organisational-group	University of Technology Sydney/Faculty of Science
pubs.organisational-group	University of Technology Sydney/Provost
pubs.organisational-group	University of Technology Sydney/Strength - CFI - Centre for Inflammation
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	2024-08-06T03:06:09Z
pubs.issue	4
pubs.publication-status	Published online
pubs.volume	7
utslib.citation.issue	4

Abstract:

Regulation of host miRNA expression is a contested node that controls the host immune response to mycobacterial infection. The host must counter subversive efforts of pathogenic mycobacteria to launch a protective immune response. Here, we examine the role of miR-126 in the zebrafish-Mycobacterium marinum infection model and identify a protective role for infection-induced miR-126 through multiple effector pathways. We identified a putative link between miR-126 and the tsc1a and cxcl12a/ccl2/ccr2 signalling axes resulting in the suppression of non-tnfa expressing macrophage accumulation at early M. marinum granulomas. Mechanistically, we found a detrimental effect of tsc1a expression that renders zebrafish embryos susceptible to higher bacterial burden and increased cell death via mTOR inhibition. We found that macrophage recruitment driven by the cxcl12a/ccl2/ccr2 signalling axis was at the expense of the recruitment of classically activated tnfa-expressing macrophages and increased cell death around granulomas. Together, our results delineate putative pathways by which infection-induced miR-126 may shape an effective immune response to M. marinum infection in zebrafish embryos.

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http://hdl.handle.net/10453/180083