Zebrafish tsc1 and cxcl12a increase susceptibility to mycobacterial infection

• Published in: Life science alliance 2024-04, Vol.7 (4), p.e202302523
• Main Authors: Wright, Kathryn, Han, Darryl Jy, Song, Renhua, de Silva, Kumudika, Plain, Karren M, Purdie, Auriol C, Shepherd, Ava, Chin, Maegan, Hortle, Elinor, Wong, Justin J-L, Britton, Warwick J, Oehlers, Stefan H
• Format: Article
• Language: English
• Subjects: Animals; Chemokine CXCL12 - metabolism; Granuloma - genetics; Macrophages; MicroRNAs - genetics; Mycobacterium Infections, Nontuberculous - genetics; Mycobacterium Infections, Nontuberculous - microbiology; Tuberous Sclerosis Complex 1 Protein - metabolism; Zebrafish; Zebrafish Proteins - metabolism
• ISSN: 2575-1077; 2575-1077
• DOI: 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- 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 and signalling axes resulting in the suppression of non- expressing macrophage accumulation at early granulomas. Mechanistically, we found a detrimental effect of 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 signalling axis was at the expense of the recruitment of classically activated -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 infection in zebrafish embryos.