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
- Publisher:
- LIFE SCIENCE ALLIANCE LLC
- Publication Type:
- Journal Article
- Citation:
- Life Sci Alliance, 2024, 7, (4), pp. e202302523
- Issue Date:
- 2024-04
Open Access
Copyright Clearance Process
- Recently Added
- In Progress
- Open Access
This item is open access.
Full metadata record
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.
Please use this identifier to cite or link to this item:
Download statistics for the last 12 months
Not enough data to produce graph