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    Antagonism of miR-328 increases the antimicrobial function of macrophages and neutrophils and rapid clearance of non-typeable Haemophilus influenzae (NTHi) from infected lung.

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    Author
    Tay, HL; Kaiko, GE; Plank, M; Li, J; Maltby, S; Essilfie, A-T; Jarnicki, A; Yang, M; Mattes, J; Hansbro, PM; ...
    Date
    2015-04
    Source Title
    PLoS Pathogens
    Publisher
    Public Library of Science (PLoS)
    University of Melbourne Author/s
    Jarnicki, Andrew
    Affiliation
    Pharmacology and Therapeutics
    Metadata
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    Document Type
    Journal Article
    Citations
    Tay, H. L., Kaiko, G. E., Plank, M., Li, J., Maltby, S., Essilfie, A. -T., Jarnicki, A., Yang, M., Mattes, J., Hansbro, P. M. & Foster, P. S. (2015). Antagonism of miR-328 increases the antimicrobial function of macrophages and neutrophils and rapid clearance of non-typeable Haemophilus influenzae (NTHi) from infected lung.. PLoS Pathog, 11 (4), pp.e1004549-. https://doi.org/10.1371/journal.ppat.1004549.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/255829
    DOI
    10.1371/journal.ppat.1004549
    Open Access at PMC
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4404141
    Abstract
    Pathogenic bacterial infections of the lung are life threatening and underpin chronic lung diseases. Current treatments are often ineffective potentially due to increasing antibiotic resistance and impairment of innate immunity by disease processes and steroid therapy. Manipulation miRNA directly regulating anti-microbial machinery of the innate immune system may boost host defence responses. Here we demonstrate that miR-328 is a key element of the host response to pulmonary infection with non-typeable haemophilus influenzae and pharmacological inhibition in mouse and human macrophages augments phagocytosis, the production of reactive oxygen species, and microbicidal activity. Moreover, inhibition of miR-328 in respiratory models of infection, steroid-induced immunosuppression, and smoke-induced emphysema enhances bacterial clearance. Thus, miRNA pathways can be targeted in the lung to enhance host defence against a clinically relevant microbial infection and offer a potential new anti-microbial approach for the treatment of respiratory diseases.

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