Nasal lavage natural killer cell function is suppressed in smokers after live attenuated influenza virus Public Deposited

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Creator
  • Herbst, Margaret C
    • Affiliation: School of Medicine, Center for Environmental Medicine, Asthma and Lung Biology, Department of Pediatrics
  • Horvath, Katherine M
    • Affiliation: School of Medicine, Curriculum in Toxicology
  • Noah, Terry
    • Affiliation: School of Medicine, Center for Environmental Medicine, Asthma and Lung Biology, Department of Pediatrics
  • Zhang, Hongtao
    • Affiliation: Gillings School of Global Public Health, Department of Biostatistics
  • Jaspers, Ilona
    • Affiliation: School of Medicine, Center for Environmental Medicine, Asthma and Lung Biology, Department of Pediatrics, Curriculum in Toxicology
  • Zhou, Haibo
    • Affiliation: School of Medicine, Center for Environmental Medicine, Asthma and Lung Biology, Gillings School of Global Public Health, Department of Biostatistics
Abstract
  • Abstract Background Modified function of immune cells in nasal secretions may play a role in the enhanced susceptibility to respiratory viruses that is seen in smokers. Innate immune cells in nasal secretions have largely been characterized by cellular differentials using morphologic criteria alone, which have successfully identified neutrophils as a significant cell population within nasal lavage fluid (NLF) cells. However, flow cytometry may be a superior method to fully characterize NLF immune cells. We therefore characterized immune cells in NLF by flow cytometry, determined the effects of live attenuated influenza virus (LAIV) on NLF and peripheral blood immune cells, and compared responses in samples obtained from smokers and nonsmokers. Methods In a prospective observational study, we characterized immune cells in NLF of nonsmokers at baseline using flow cytometry and immunohistochemistry. Nonsmokers and smokers were inoculated with LAIV on day 0 and serial nasal lavages were collected on days 1-4 and day 9 post-LAIV. LAIV-induced changes of NLF cells were characterized using flow cytometry. Cell-free NLF was analyzed for immune mediators by bioassay. Peripheral blood natural killer (NK) cells from nonsmokers and smokers at baseline were stimulated in vitro with LAIV followed by flow cytometric and mediator analyses. Results CD45(+)CD56(-)CD16(+) neutrophils and CD45(+)CD56(+) NK cells comprised median 4.62% (range 0.33-14.52) and 23.27% (18.29-33.97), respectively, of non-squamous NLF cells in nonsmokers at baseline. LAIV did not induce changes in total NK cell or neutrophil percentages in either nonsmokers or smokers. Following LAIV inoculation, CD16(+) NK cell percentages and granzyme B levels increased in nonsmokers, and these effects were suppressed in smokers. LAIV inoculation enhanced expression of activating receptor NKG2D and chemokine receptor CXCR3 on peripheral blood NK cells from both nonsmokers and smokers in vitro but did not induce changes in CD16(+) NK cells or granzyme B activity in either group. Conclusions These data are the first to identify NK cells as a major immune cell type in the NLF cell population and demonstrate that mucosal NK cell cytotoxic function is suppressed in smokers following LAIV. Altered NK cell function in smokers suggests a potential mechanism that may enhance susceptibility to respiratory viruses.
Date of publication
Identifier
  • 21816072
  • doi:10.1186/1465-9921-12-102
Resource type
  • Article
Rights statement
  • In Copyright
Rights holder
  • Katherine M Horvath et al.; licensee BioMed Central Ltd.
License
Journal title
  • Respiratory Research
Journal volume
  • 12
Journal issue
  • 1
Page start
  • 102
Language
  • English
Is the article or chapter peer-reviewed?
  • Yes
ISSN
  • 1465-9921
Bibliographic citation
  • Respiratory Research. 2011 Aug 04;12(1):102
Access
  • Open Access
Publisher
  • BioMed Central Ltd
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