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Clinical & Experimental Allergy

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

Authors

  • Y.-S. Kim,

    1. Department of Life Science and Division of Molecular and Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea
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    • These authors contributed equally to this work.
  • E.-J. Choi,

    1. Department of Life Science and Division of Molecular and Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea
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    • These authors contributed equally to this work.
  • W.-H. Lee,

    1. Department of Life Science and Division of Molecular and Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea
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  • S.-J. Choi,

    1. Department of Life Science and Division of Molecular and Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea
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  • T.-Y. Roh,

    1. Department of Life Science and Division of Molecular and Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea
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  • J. Park,

    1. Department of Mechanical Engineering, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea
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  • Y.-K. Jee,

    1. Department of Internal Medicine, Dankook University College of Medicine, Cheonan, Republic of Korea
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  • Z. Zhu,

    1. Asthma and Allergy Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA
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  • Y.-Y. Koh,

    1. Department of Pediatrics, Seoul National University College of Medicine, Seoul, Republic of Korea
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  • Y. S. Gho,

    Corresponding author
    • Department of Life Science and Division of Molecular and Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea
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  • Y.-K. Kim

    Corresponding author
    • Department of Life Science and Division of Molecular and Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea
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Correspondence: Y.-K. Kim, Department of Life Science and Division of Molecular and Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea. E-mail: juinea@postech.ac.kr and Y. S. Gho, E-mail: ysgho@postech.ac.kr

Summary

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.

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