Antagonism of miR-328 Increases the Antimicrobial Function of Macrophages and Neutrophils and Rapid Clearance of Non-typeable Haemophilus Influenzae (NTHi) from Infected Lung

Tay, HL; Kaiko, GE; Plank, M; Li, JJ; Maltby, S; Essilfie, AT; Jarnicki, A; Yang, M; Mattes, J; Hansbro, PM; Foster, PS

Antagonism of miR-328 Increases the Antimicrobial Function of Macrophages and Neutrophils and Rapid Clearance of Non-typeable Haemophilus Influenzae (NTHi) from Infected Lung

Tay, HL Kaiko, GE Plank, M Li, JJ Maltby, S Essilfie, AT Jarnicki, A Yang, M Mattes, J Hansbro, PM

Foster, PS

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Publication Type:: Journal Article
Citation:: PLoS Pathogens, 2015, 11 (4)
Issue Date:: 2015-01-01

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Field	Value	Language
dc.contributor.author	Tay, HL	en_US
dc.contributor.author	Kaiko, GE	en_US
dc.contributor.author	Plank, M	en_US
dc.contributor.author	Li, JJ	en_US
dc.contributor.author	Maltby, S	en_US
dc.contributor.author	Essilfie, AT	en_US
dc.contributor.author	Jarnicki, A	en_US
dc.contributor.author	Yang, M	en_US
dc.contributor.author	Mattes, J	en_US
dc.contributor.author	Hansbro, PM https://orcid.org/0000-0002-4741-3035	en_US
dc.contributor.author	Foster, PS	en_US
dc.date.available	2014-11-01	en_US
dc.date.issued	2015-01-01	en_US
dc.identifier.citation	PLoS Pathogens, 2015, 11 (4)	en_US
dc.identifier.issn	1553-7366	en_US
dc.identifier.uri	http://hdl.handle.net/10453/128826
dc.description.abstract	© 2015 Tay et al. 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.	en_US
dc.relation.ispartof	PLoS Pathogens	en_US
dc.relation.isbasedon	10.1371/journal.ppat.1004549	en_US
dc.subject.classification	Virology	en_US
dc.subject.mesh	Neutrophils	en_US
dc.subject.mesh	Macrophages	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Mice, Inbred BALB C	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Mice	en_US
dc.subject.mesh	Haemophilus influenzae	en_US
dc.subject.mesh	Haemophilus Infections	en_US
dc.subject.mesh	Respiratory Tract Infections	en_US
dc.subject.mesh	MicroRNAs	en_US
dc.subject.mesh	Fluorescent Antibody Technique	en_US
dc.subject.mesh	Oligonucleotide Array Sequence Analysis	en_US
dc.subject.mesh	Flow Cytometry	en_US
dc.subject.mesh	Reverse Transcriptase Polymerase Chain Reaction	en_US
dc.subject.mesh	Male	en_US
dc.title	Antagonism of miR-328 Increases the Antimicrobial Function of Macrophages and Neutrophils and Rapid Clearance of Non-typeable Haemophilus Influenzae (NTHi) from Infected Lung	en_US
dc.type	Journal Article
utslib.citation.volume	4	en_US
utslib.citation.volume	11	en_US
utslib.for	0605 Microbiology	en_US
utslib.for	1107 Immunology	en_US
utslib.for	1108 Medical Microbiology	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
utslib.copyright.status	open_access
pubs.issue	4	en_US
pubs.publication-status	Published	en_US
pubs.volume	11	en_US

Abstract:

© 2015 Tay et al. 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.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/128826