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. 2015 Apr 20;11(4):e1004549. doi: 10.1371/journal.ppat.1004549. eCollection 2015 Apr.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Haemophilus Infections / genetics
  • Haemophilus Infections / immunology*
  • Haemophilus influenzae
  • Humans
  • Macrophages / immunology*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • MicroRNAs / antagonists & inhibitors*
  • Neutrophils / immunology*
  • Oligonucleotide Array Sequence Analysis
  • Respiratory Tract Infections / genetics
  • Respiratory Tract Infections / immunology*
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • MIRN328 microRNA, human
  • MIRN328 microRNA, mouse
  • MicroRNAs

Grant support

This study was supported by the National Health Medical Research Council (NH&MRC). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.