Host resistance to lung infection mediated by major vault protein in epithelial cells

Science. 2007 Jul 6;317(5834):130-2. doi: 10.1126/science.1142311.

Abstract

The airway epithelium plays an essential role in innate immunity to lung pathogens. Ribonucleoprotein particles primarily composed of major vault protein (MVP) are highly expressed in cells that encounter xenobiotics. However, a clear biologic function for MVP is not established. We report here that MVP is rapidly recruited to lipid rafts when human lung epithelial cells are infected with Pseudomonas aeruginosa, and maximal recruitment is dependent on bacterial binding to the cystic fibrosis transmembrane conductance regulator. MVP was also essential for optimal epithelial cell internalization and clearance of P. aeruginosa. These results suggest that MVP makes a substantial contribution to epithelial cell-mediated resistance to infection.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics
  • Cystic Fibrosis Transmembrane Conductance Regulator / metabolism
  • Epithelial Cells / metabolism
  • Epithelial Cells / microbiology
  • Humans
  • Immunity, Innate
  • Lung / immunology
  • Lung / microbiology
  • Lung Diseases / immunology*
  • Lung Diseases / metabolism
  • Lung Diseases / microbiology
  • Membrane Microdomains / metabolism
  • Mice
  • Pseudomonas Infections / immunology*
  • Pseudomonas Infections / metabolism
  • Pseudomonas Infections / microbiology
  • Pseudomonas aeruginosa / immunology*
  • Pseudomonas aeruginosa / metabolism
  • RNA, Small Interfering / genetics
  • Respiratory Mucosa / immunology
  • Respiratory Mucosa / metabolism*
  • Respiratory Mucosa / microbiology*
  • Signal Transduction
  • Vault Ribonucleoprotein Particles / physiology*

Substances

  • RNA, Small Interfering
  • Vault Ribonucleoprotein Particles
  • major vault protein
  • Cystic Fibrosis Transmembrane Conductance Regulator