Epithelial cells from smokers modify dendritic cell responses in the context of influenza infection

Am J Respir Cell Mol Biol. 2011 Aug;45(2):237-45. doi: 10.1165/rcmb.2010-0190OC. Epub 2010 Oct 8.


Epidemiologic evidence suggests that cigarette smoking is a risk factor for infection with influenza, but the mechanisms underlying this susceptibility remain unknown. To ascertain if airway epithelial cells from smokers demonstrate a decreased ability to orchestrate an influenza-induced immune response, we established a model using differentiated nasal epithelial cells (NECs) from nonsmokers and smokers, co-cultured with peripheral blood monocyte-derived dendritic cells (mono-DCs) from nonsmokers. NEC/mono-DC co-cultures were infected with influenza A virus and analyzed for influenza-induced immune responses 24 hours after infection. We observed that NECs from smokers, as well as mono-DCs co-cultured with NECs from smokers, exhibited suppressed influenza-induced, interferon-related proteins interferon regulatory factor-7, Toll-like receptor-3, and retinoic acid inducible gene-1, likely because of the suppressed production of IFNα from the NECs of smokers. Furthermore, NEC/mono-DC co-cultures using NECs from smokers exhibited suppressed concentrations of T-cell/natural killer cell chemokine interferon gamma-induced protein 10 (IP-10) after infection with influenza, indicating that NECs from smokers may skew early influenza-induced Th1 responses. In contrast, NEC/mono-DC co-cultures using NEC from smokers contained increased influenza-induced concentrations of the Th2 chemokine thymic stromal lymphopoeitin (TSLP). In addition, NECs from smokers cultured alone had increased influenza-induced concentrations of the Th2 chemokine thymus and activation-regulated chemokine (TARC). Using this model, we demonstrated that in the context of infection with influenza, NECs obtained from smokers create an overall cytokine microenvironment that suppresses the interferon-mediated Th1 response and enhances the TSLP-TARC-mediated Th2 response, with the potential to modify the responses of DCs. Smoking-induced alterations in the Th1/Th2 balance may play a role in developing underlying susceptibilities to respiratory viral infections, and may also promote the likelihood of acquiring Th2 proallergic diseases.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Cell Differentiation
  • Cells, Cultured
  • Coculture Techniques
  • Cytokines / genetics
  • Cytokines / metabolism
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Dendritic Cells / virology
  • Epithelial Cells / immunology*
  • Epithelial Cells / metabolism
  • Epithelial Cells / virology
  • Humans
  • Influenza A virus / pathogenicity
  • Influenza, Human / immunology*
  • Influenza, Human / metabolism
  • Influenza, Human / virology
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / metabolism
  • Killer Cells, Natural / virology
  • Nasal Mucosa / immunology*
  • Nasal Mucosa / metabolism
  • Nasal Mucosa / virology
  • RNA, Messenger / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Smoking*
  • Th1 Cells / immunology*
  • Th1 Cells / metabolism
  • Th1 Cells / virology
  • Th2 Cells / immunology*
  • Th2 Cells / metabolism
  • Th2 Cells / virology


  • Cytokines
  • RNA, Messenger