PUBLICATION
Mycobacterial infection-induced miR-206 inhibits protective neutrophil recruitment via the CXCL12/CXCR4 signalling axis
- Authors
- Wright, K., de Silva, K., Plain, K.M., Purdie, A.C., Blair, T.A., Duggin, I.G., Britton, W.J., Oehlers, S.H.
- ID
- ZDB-PUB-210409-9
- Date
- 2021
- Source
- PLoS pathogens 17: e1009186 (Journal)
- Registered Authors
- Oehlers, Stefan
- Keywords
- none
- MeSH Terms
-
- Animals
- Chemokine CXCL12/immunology
- Chemokine CXCL12/metabolism*
- Gene Knockdown Techniques/methods
- MicroRNAs/genetics*
- Mycobacterium Infections, Nontuberculous/genetics
- Mycobacterium Infections, Nontuberculous/immunology
- Mycobacterium marinum/metabolism
- Neutrophil Infiltration/immunology*
- Receptors, CXCR4/immunology
- Receptors, CXCR4/metabolism*
- Signal Transduction/genetics
- Signal Transduction/immunology
- Zebrafish/immunology
- PubMed
- 33826679 Full text @ PLoS Pathog.
Citation
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.
Abstract
Pathogenic 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping