Zebrafish tsc1 and cxcl12a increase susceptibility to mycobacterial infection.,Life Science Alliance

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Zebrafish tsc1 and cxcl12a increase susceptibility to mycobacterial infection.
Life Science Alliance ( IF 4.4 ) Pub Date : 2024-02-02 , DOI: 10.26508/lsa.202302523
Kathryn Wright _{1,

2,

3,

4} , Darryl JY Han ₅ , Renhua Song _{4,

6} , Kumudika de Silva ₂ , Karren M Plain ₂ , Auriol C Purdie ₂ , Ava Shepherd ₃ , Maegan Chin ₃ , Elinor Hortle _{1,

4,

7} , Justin J-L Wong _{4,

6} , Warwick J Britton _{1,

4,

8} , Stefan H Oehlers _{1,

4,

5}

Affiliation

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.

更新日期：2024-02-02

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