Extracellular vesicles, especially derived from Gram-negative bacteria, in indoor dust induce neutrophilic pulmonary inflammation associated with both Th1 and Th17 cell responses

Clin Exp Allergy. 2013 Apr;43(4):443-54. doi: 10.1111/cea.12085.

Abstract

Background: Many bacterial components in indoor dust can evoke inflammatory pulmonary diseases. Bacteria secrete nanometre-sized vesicles into the extracellular milieu, but it remains to be determined whether bacteria-derived extracellular vesicles in indoor dust are pathophysiologically related to inflammatory pulmonary diseases.

Objective: To evaluate whether extracellular vesicles (EV) in indoor air are related to the pathogenesis of pulmonary inflammation and/or asthma.

Methods: Indoor dust was collected from a bed mattress in an apartment. EV were prepared by sequential ultrafiltration and ultracentrifugation. Innate and adaptive immune responses were evaluated after airway exposure of EV.

Results: Repeated intranasal application of indoor-dust-induced neutrophilic pulmonary inflammation accompanied by lung infiltration of both Th1 and Th17 cells. EV 50-200 nm in diameter were present (102.5 μg protein concentration/g dust) in indoor dust. These vesicles were internalized by airway epithelial cells and alveolar macrophages, and this process was blocked by treatment of polymyxin B (an antagonist of lipopolysaccharide, an outer-membrane component of Gram-negative bacteria). Intranasal application of 0.1 or 1 μg of these vesicles for 4 weeks elicited neutrophilic pulmonary inflammation. This phenotype was accompanied by lung infiltration of both Th1 and Th17 cells, which were reversed by treatment of polymyxin B. Serum dust EV-reactive IgG1 levels were significantly higher in atopic children with asthma than in atopic healthy children and those with rhinitis or dermatitis.

Conclusion & clinical relevance: Indoor dust EV, especially derived from Gram-negative bacteria, is a possible causative agent of neutrophilic airway diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity
  • Animals
  • Cell Line
  • Cell-Derived Microparticles / metabolism*
  • Child
  • Dust / immunology*
  • Gram-Negative Bacteria / immunology
  • Gram-Negative Bacteria / metabolism*
  • Humans
  • Immunity, Innate
  • Immunoglobulin E / blood
  • Immunoglobulin G / blood
  • Inflammation Mediators / metabolism
  • Lipopolysaccharide Receptors / metabolism
  • Lipopolysaccharides / immunology
  • Lung / immunology
  • Lung / pathology
  • Macrophages / immunology
  • Macrophages / metabolism
  • Mice
  • Neutrophils / immunology*
  • Pneumonia / etiology*
  • Th1 Cells / immunology*
  • Th17 Cells / immunology*

Substances

  • Dust
  • Immunoglobulin G
  • Inflammation Mediators
  • Lipopolysaccharide Receptors
  • Lipopolysaccharides
  • Immunoglobulin E