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

Y. S. Kim, E. J. Choi, W. H. Lee, S. J. Choi, T. Y. Roh, J. Park, Y. K. Jee, Z. Zhu, Y. Y. Koh, Y. S. Gho, Y. K. Kim

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)443-454
Number of pages12
JournalClinical and Experimental Allergy
Volume43
Issue number4
DOIs
StatePublished - Apr 2013

Keywords

  • Asthma
  • Extracellular vesicles
  • IFN-gamma
  • IL-17
  • Neutrophilic inflammation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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