Mycobacterial infection-induced miR-206 inhibits protective neutrophil recruitment via the CXCL12/CXCR4 signalling axis
| العنوان: | Mycobacterial infection-induced miR-206 inhibits protective neutrophil recruitment via the CXCL12/CXCR4 signalling axis |
|---|---|
| المؤلفون: | Kumudika de Silva, Karren M. Plain, Warwick J. Britton, Iain G. Duggin, Kathryn Wright, Stefan H. Oehlers, Auriol C. Purdie, Tamika A. Blair |
| المصدر: | PLoS Pathogens PLoS Pathogens, Vol 17, Iss 4, p e1009186 (2021) |
| بيانات النشر: | PUBLIC LIBRARY SCIENCE, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Embryology, Neutrophils, 0605 Microbiology, 1107 Immunology, 1108 Medical Microbiology, Pathology and Laboratory Medicine, Biochemistry, CXCR4, Diagnostic Radiology, White Blood Cells, 0302 clinical medicine, Animal Cells, Medicine and Health Sciences, CRISPR, Biology (General), Receptor, Zebrafish, 0303 health sciences, Gene knockdown, biology, Radiology and Imaging, Infection Imaging, Eukaryota, Animal Models, Hedgehog signaling pathway, Bacterial Pathogens, Cell biology, Actinobacteria, Nucleic acids, Neutrophil Infiltration, Experimental Organism Systems, Osteichthyes, Medical Microbiology, Gene Knockdown Techniques, 030220 oncology & carcinogenesis, Vertebrates, Granulomas, Cellular Types, Pathogens, Signal Transduction, Research Article, Receptors, CXCR4, QH301-705.5, Imaging Techniques, Immune Cells, Immunology, Mycobacterium Infections, Nontuberculous, Research and Analysis Methods, Microbiology, 03 medical and health sciences, Model Organisms, Immune system, Downregulation and upregulation, Diagnostic Medicine, Virology, microRNA, Genetics, Animals, Non-coding RNA, Microbial Pathogens, Molecular Biology, 030304 developmental biology, Natural antisense transcripts, Blood Cells, Bacteria, Embryos, Organisms, Biology and Life Sciences, Mycobacteria, Cell Biology, RC581-607, biology.organism_classification, Chemokine CXCL12, Gene regulation, MicroRNAs, Fish, Infectious disease (medical specialty), Mycobacterium marinum, Animal Studies, RNA, Parasitology, Gene expression, Immunologic diseases. Allergy, Zoology, Mycobacterium Tuberculosis, Developmental Biology |
| الوصف: | 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. Author summary Mycobacterial infections cause significant disease burden to humans and animals, the most widely known example being tuberculosis which has killed more humans than any other infectious disease throughout history. Infectious mycobacteria are highly evolved to hijack host processes, including the very immune cells tasked with destroying them. MicroRNAs are host molecules that control wide-ranging programs of host gene expression and are important in the immune response to infections. Here we use the zebrafish model of mycobacterial infection to determine the role of the infection-induced microRNA miR-206 in the host response to infection. We found pathogenic mycobacteria trigger the host to produce more miR-206 in order to suppress the otherwise protective recruitment of neutrophils to sites of infection via the host Cxcl12/Cxcr4 signalling pathway. Our study provides new insight into the role of mycobacterial infection-induced miR-206 function in the context of a whole host. |
| وصف الملف: | Electronic-eCollection; application/pdf |
| اللغة: | English |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ef23bf90ae3e131d0ba530a68d646070 https://hdl.handle.net/10453/149779 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....ef23bf90ae3e131d0ba530a68d646070 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |