|ZFIN ID: ZDB-PUB-210409-9|
Mycobacterial infection-induced miR-206 inhibits protective neutrophil recruitment via the CXCL12/CXCR4 signalling axis
Wright, K., de Silva, K., Plain, K.M., Purdie, A.C., Blair, T.A., Duggin, I.G., Britton, W.J., Oehlers, S.H.
|Source:||PLoS pathogens 17: e1009186 (Journal)|
|Registered Authors:||Oehlers, Stefan|
|PubMed:||33826679 Full text @ PLoS Pathog.|
Wright, K., de Silva, K., Plain, K.M., Purdie, A.C., Blair, T.A., Duggin, I.G., Britton, W.J., Oehlers, S.H. (2021) Mycobacterial infection-induced miR-206 inhibits protective neutrophil recruitment via the CXCL12/CXCR4 signalling axis. PLoS pathogens. 17:e1009186.
ABSTRACTPathogenic mycobacteria actively dysregulate protective host immune signalling pathways during infection to drive the formation of permissive granuloma microenvironments. Dynamic regulation of host microRNA (miRNA) expression is a conserved feature of mycobacterial infections across host-pathogen pairings. Here we examine the role of miR-206 in the zebrafish model of Mycobacterium marinum infection, which allows investigation of the early stages of granuloma formation. We find miR-206 is upregulated following infection by pathogenic M. marinum and that antagomir-mediated knockdown of miR-206 is protective against infection. We observed striking upregulation of cxcl12a and cxcr4b in infected miR-206 knockdown zebrafish embryos and live imaging revealed enhanced recruitment of neutrophils to sites of infection. We used CRISPR/Cas9-mediated knockdown of cxcl12a and cxcr4b expression and AMD3100 inhibition of Cxcr4 to show that the enhanced neutrophil response and reduced bacterial burden caused by miR-206 knockdown was dependent on the Cxcl12/Cxcr4 signalling axis. Together, our data illustrate a pathway through which pathogenic mycobacteria induce host miR-206 expression to suppress Cxcl12/Cxcr4 signalling and prevent protective neutrophil recruitment to granulomas.
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