Electronic cigarette inhalation alters innate immunity and airway cytokines while increasing the virulence of colonizing bacteria

Abstract

Electronic (e)-cigarette use is rapidly rising, with 20 % of Americans ages 25–44 now using these drug delivery devices. E-cigarette users expose their airways, cells of host defense, and colonizing bacteria to e-cigarette vapor (EV). Here, we report that exposure of human epithelial cells at the air–liquid interface to fresh EV (vaped from an e-cigarette device) resulted in dose-dependent cell death. After exposure to EV, cells of host defense—epithelial cells, alveolar macrophages, and neutrophils—had reduced antimicrobial activity against Staphylococcus aureus (SA). Mouse inhalation of EV for 1 h daily for 4 weeks led to alterations in inflammatory markers within the airways and elevation of an acute phase reactant in serum. Upon exposure to e-cigarette vapor extract (EVE), airway colonizer SA had increased biofilm formation, adherence and invasion of epithelial cells, resistance to human antimicrobial peptide LL-37, and up-regulation of virulence genes. EVE-exposed SA were more virulent in a mouse model of pneumonia. These data suggest that e-cigarettes may be toxic to airway cells, suppress host defenses, and promote inflammation over time, while also promoting virulence of colonizing bacteria.

Key message

  • Acute exposure to e-cigarette vapor (EV) is cytotoxic to airway cells in vitro.

  • Acute exposure to EV decreases macrophage and neutrophil antimicrobial function.

  • Inhalation of EV alters immunomodulating cytokines in the airways of mice.

  • Inhalation of EV leads to increased markers of inflammation in BAL and serum.

  • Staphylococcus aureus become more virulent when exposed to EV.

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Acknowledgments

This work was supported by the VA Career Development Award (CDA)-2, award no. 1IK2BX001313, PI Crotty Alexander, from the U.S. Department of Veterans Affairs, Biomedical Laboratory Research and Development (BLR&D) Program. Thank you to Drs. Ross Corriden and Simon Döhrmann for their technical support. Thank you to Dr. Atul Malhotra for his guidance and support.

Author contributions

JHH, EM, WMO, SB, SD, and LCA designed the research. JHH, ML, KS, SE, SD, EM, DM, AM, SD, SB, WMO, and LCA performed the research and analyzed the data. JHH, SE, SB, ML, DTP, WMO, and LCA performed statistical analyses and edited the paper. JHH, SD, SB, and LCA wrote the paper.

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Correspondence to Laura E. Crotty Alexander.

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Hwang, J.H., Lyes, M., Sladewski, K. et al. Electronic cigarette inhalation alters innate immunity and airway cytokines while increasing the virulence of colonizing bacteria. J Mol Med 94, 667–679 (2016). https://doi.org/10.1007/s00109-016-1378-3

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Keywords

  • E-cigarette vapor
  • Staphylococcal virulence
  • Cytotoxicity
  • Inflammatory lung disease
  • Antimicrobial peptide LL-37
  • MRSA pneumonia