Electronic cigarette inhalation alters innate immunity and airway cytokines while increasing the virulence of colonizing bacteria
- 3.4k Downloads
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.
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.
KeywordsE-cigarette vapor Staphylococcal virulence Cytotoxicity Inflammatory lung disease Antimicrobial peptide LL-37 MRSA pneumonia
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.
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.
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no competing interests.
- 1.King BA (2013) Notes from the field: electronic cigarette use among middle and high school students—United States, 2011-2012 Morbidity and Mortality Weekly Report (MMWR) Centers for Disease Control and Prevention (CDC), Atlanta, pp. 729–730.Google Scholar
- 5.Bostean G, Trinidad DR, McCarthy WJ (2015) E-cigarette use among never-smoking California students. American journal of public health: e1-e3. DOI 10.2105/AJPH.2015.302899
- 10.Bauguess AJ (2014) How to make your own e-liquid (e-juice). ecigvape.com.Google Scholar
- 30.Yang ES, Tan J, Eells S, Rieg G, Tagudar G, Miller LG (2010) Body site colonization in patients with community-associated methicillin-resistant Staphylococcus aureus and other types of S. aureus skin infections. Clin Microbiol Infect: Off Publ Eur Soc Clin Microbiol Infect Dis 16:425–431CrossRefGoogle Scholar
- 37.Farsalinos KE, Romagna G, Allifranchini E, Ripamonti E, Bocchietto E, Todeschi S, Tsiapras D, Kyrzopoulos S, Voudris V (2013) Comparison of the cytotoxic potential of cigarette smoke and electronic cigarette vapour extract on cultured myocardial cells. Int J Environ Res Public Health 10(10):5146–5162CrossRefPubMedPubMedCentralGoogle Scholar
- 43.Papanikolaou IC, Boki KA, Giamarellos-Bourboulis EJ, Kotsaki A, Kagouridis K, Karagiannidis N, Polychronopoulos VS (2015) Innate immunity alterations in idiopathic interstitial pneumonias and rheumatoid arthritis-associated interstitial lung diseases. Immunol Lett 163:179–186CrossRefPubMedGoogle Scholar
- 45.Sussan TE, Gajghate S, Thimmulappa RK, Ma J, Kim JH, Sudini K, Consolini N, Cormier SA, Lomnicki S, Hasan F et al (2015) Exposure to electronic cigarettes impairs pulmonary anti-bacterial and anti-viral defenses in a mouse model. PLoS ONE 10(2), e0116861. doi: 10.1371/journal.pone.0116861 CrossRefPubMedPubMedCentralGoogle Scholar
- 48.Hamilton SM, Bryant AE, Carroll KC, Lockary V, Ma Y, McIndoo E, Miller LG, Perdreau-Remington F, Pullman J, Risi GF et al (2007) In vitro production of panton-valentine leukocidin among strains of methicillin-resistant Staphylococcus aureus causing diverse infections. Clin Infect Dis: Off Publ Infect Dis Soc Am 45:1550–1558CrossRefGoogle Scholar
- 50.Gillet Y, Issartel B, Vanhems P, Fournet JC, Lina G, Bes M, Vandenesch F, Piemont Y, Brousse N, Floret D et al (2002) Association between Staphylococcus aureus strains carrying gene for Panton-Valentine leukocidin and highly lethal necrotising pneumonia in young immunocompetent patients. Lancet 359:753–759CrossRefPubMedGoogle Scholar
- 51.Crotty Alexander LE, Maisey HC, Timmer AM, Rooijakkers SH, Gallo RL, von Kockritz-Blickwede M, Nizet V (2010) M1T1 group A streptococcal pili promote epithelial colonization but diminish systemic virulence through neutrophil extracellular entrapment. J Mol Med 88:371–381CrossRefPubMedPubMedCentralGoogle Scholar