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.
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.
authors.affiliation: Priority Research Centre for Asthma and Respiratory Disease, Department of Microbiology and Immunology, School of Pharmacy and Biomedical Sciences, Faculty of Health and Hunter Medical Research Institute, University of Newcastle, Newcastle, Australia.
authors.forename: Hock L
authors.initials: HL
authors.lastname: Tay
authors.affiliation: Priority Research Centre for Asthma and Respiratory Disease, Department of Microbiology and Immunology, School of Pharmacy and Biomedical Sciences, Faculty of Health and Hunter Medical Research Institute, University of Newcastle, Newcastle, Australia.
authors.forename: Gerard E
authors.initials: GE
authors.lastname: Kaiko
authors.affiliation: Priority Research Centre for Asthma and Respiratory Disease, Department of Microbiology and Immunology, School of Pharmacy and Biomedical Sciences, Faculty of Health and Hunter Medical Research Institute, University of Newcastle, Newcastle, Australia.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Plank
authors.affiliation: Priority Research Centre for Asthma and Respiratory Disease, Department of Microbiology and Immunology, School of Pharmacy and Biomedical Sciences, Faculty of Health and Hunter Medical Research Institute, University of Newcastle, Newcastle, Australia.
authors.forename: JingJing
authors.initials: J
authors.lastname: Li
authors.affiliation: Priority Research Centre for Asthma and Respiratory Disease, Department of Microbiology and Immunology, School of Pharmacy and Biomedical Sciences, Faculty of Health and Hunter Medical Research Institute, University of Newcastle, Newcastle, Australia.
authors.forename: Steven
authors.initials: S
authors.lastname: Maltby
authors.affiliation: Priority Research Centre for Asthma and Respiratory Disease, Department of Microbiology and Immunology, School of Pharmacy and Biomedical Sciences, Faculty of Health and Hunter Medical Research Institute, University of Newcastle, Newcastle, Australia.
authors.forename: Ama-Tawiah
authors.initials: AT
authors.lastname: Essilfie
authors.affiliation: Priority Research Centre for Asthma and Respiratory Disease, Department of Microbiology and Immunology, School of Pharmacy and Biomedical Sciences, Faculty of Health and Hunter Medical Research Institute, University of Newcastle, Newcastle, Australia.
authors.forename: Andrew
authors.initials: A
authors.lastname: Jarnicki
authors.affiliation: Priority Research Centre for Asthma and Respiratory Disease, Department of Microbiology and Immunology, School of Pharmacy and Biomedical Sciences, Faculty of Health and Hunter Medical Research Institute, University of Newcastle, Newcastle, Australia.
authors.forename: Ming
authors.initials: M
authors.lastname: Yang
authors.affiliation: Priority Research Centre for Asthma and Respiratory Disease, Discipline of Paediatrics and Child Health, School of Medicine and Public Health, Faculty of Health and Hunter Medical Research Institute, University of Newcastle, Newcastle, Australia.
authors.forename: Joerg
authors.initials: J
authors.lastname: Mattes
authors.affiliation: Priority Research Centre for Asthma and Respiratory Disease, Department of Microbiology and Immunology, School of Pharmacy and Biomedical Sciences, Faculty of Health and Hunter Medical Research Institute, University of Newcastle, Newcastle, Australia.
authors.forename: Philip M
authors.initials: PM
authors.lastname: Hansbro
authors.affiliation: Priority Research Centre for Asthma and Respiratory Disease, Department of Microbiology and Immunology, School of Pharmacy and Biomedical Sciences, Faculty of Health and Hunter Medical Research Institute, University of Newcastle, Newcastle, Australia.
authors.forename: Paul S
authors.initials: PS
authors.lastname: Foster
mesh_terms: D000818:Animals; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006192:Haemophilus Infections / Q000235:genetics / Q000276:immunology*; D006193:Haemophilus influenzae; D006801:Humans; D008264:Macrophages / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000037:antagonists & inhibitors*; D009504:Neutrophils / Q000276:immunology*; D020411:Oligonucleotide Array Sequence Analysis; D012141:Respiratory Tract Infections / Q000235:genetics / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C548170:MIRN328 microRNA, human; C548169:MIRN328 microRNA, mouse; D035683:MicroRNAs