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 Pathogens

Hock L. Tay¹  Gerard E. Kaiko¹  Ama-Tawiah Essilfie¹  Maximilian Plank¹  Joerg Mattes¹  Philip M. Hansbro¹  Andrew Jarnicki¹  JingJing Li¹  Steven Maltby¹  Ming Yang² 

[1] 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;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

关键词: Macrophages;    Neutrophils;    MicroRNAs;    Respiratory infections;    Phagocytosis;    Bacterial diseases;    Cell enumeration techniques;    Flow cytometry;   

DOI  :  10.1371/journal.ppat.1004549

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY