Zebrafish tsc1 and cxcl12a increase susceptibility to mycobacterial infection

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Zebrafish tsc1 and cxcl12a increase susceptibility to mycobacterial infection
Zebrafish tsc1 and cxcl12a increase susceptibility to mycobacterial infection
Journal Title:
Life Science Alliance
Publication Date:
02 February 2024
Wright, K., Han, D. J., Song, R., de Silva, K., Plain, K. M., Purdie, A. C., Shepherd, A., Chin, M., Hortle, E., Wong, J. J.-L., Britton, W. J., & Oehlers, S. H. (2024). Zebrafishtsc1andcxcl12aincrease susceptibility to mycobacterial infection. Life Science Alliance, 7(4), e202302523. https://doi.org/10.26508/lsa.202302523
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 marinuminfection model and identify a protective role for infection-induced miR-126 through multiple effector pathways. We identified a putative link between miR-126 and thetsc1aandcxcl12a/ccl2/ccr2signalling axes resulting in the suppression of non-tnfaexpressing macrophage accumulation at earlyM. marinumgranulomas. Mechanistically, we found a detrimental effect oftsc1aexpression that renders zebrafish embryos susceptible to higher bacterial burden and increased cell death via mTOR inhibition. We found that macrophage recruitment driven by thecxcl12a/ccl2/ccr2signalling axis was at the expense of the recruitment of classically activatedtnfa-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 toM. marinuminfection in zebrafish embryos.
License type:
Attribution 4.0 International (CC BY 4.0)
Funding Info:
This research is supported by core funding from: ID Labs
Grant Reference no. : Core

The work was supported by 1) Meat and Livestock Australia Grant (P.PSH.0813) 2) Higher Degree Research scholarship (P.PSH.0813) 3) Centenary Institute Summer Scholarship 4) University of Sydney Fellowship (G197581) 5) NSW Ministry of Health under the NSW Health Early-Mid Career Fellowships Scheme (H18/31086) t 6) National Health and Medical Research Council Centre of Research Excellence in Tuberculosis Control (APP1153493) and the University of Sydney DVCR