Exposure to cigarette smoke inhibits the pulmonary T-cell response to influenza virus and mycobacterium tuberculosis

Yan Feng, Ying Kong, Peter F. Barnes, Fang Fang Huang, Peter Klucar, Xisheng Wang, Buka Samten, Mayami Sengupta, Bruce MacHona, Ruben Donis, Amy R. Tvinnereim, Homayoun Shams

Research output: Contribution to journalArticle

81 Scopus citations

Abstract

Smoking is associated with increased susceptibility to tuberculosis and influenza. However, little information is available on the mechanisms underlying this increased susceptibility. Mice were left unexposed or were exposed to cigarette smoke and then infected with Mycobacterium tuberculosis by aerosol or influenza A by intranasal infection. Some mice were given a DNA vaccine encoding an immunogenic M. tuberculosis protein. Gamma interferon (IFN-γ) production by T cells from the lungs and spleens was measured. Cigarette smoke exposure inhibited the lung T-cell production of IFN-γ during stimulation in vitro with anti-CD3, after vaccination with a construct expressing an immunogenic mycobacterial protein, and during infection with M. tuberculosis and influenza A virus in vivo. Reduced IFN-γ production was mediated through the decreased phosphorylation of transcription factors that positively regulate IFN-γ expression. Cigarette smoke exposure increased the bacterial burden in mice infected with M. tuberculosis and increased weight loss and mortality in mice infected with influenza virus. This study provides the first demonstration that cigarette smoke exposure directly inhibits the pulmonary T-cell response to M. tuberculosis and influenza virus in a physiologically relevant animal model, increasing susceptibility to both pathogens.

Original languageEnglish (US)
Pages (from-to)229-237
Number of pages9
JournalInfection and immunity
Volume79
Issue number1
DOIs
StatePublished - Jan 1 2011

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

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    Feng, Y., Kong, Y., Barnes, P. F., Huang, F. F., Klucar, P., Wang, X., Samten, B., Sengupta, M., MacHona, B., Donis, R., Tvinnereim, A. R., & Shams, H. (2011). Exposure to cigarette smoke inhibits the pulmonary T-cell response to influenza virus and mycobacterium tuberculosis. Infection and immunity, 79(1), 229-237. https://doi.org/10.1128/IAI.00709-10