Exposure to cigarette smoke inhibits the pulmonary T-cell response to influenza virus and Mycobacterium tuberculosis.
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.
Feng
Yan
Y
Center for Pulmonary and Infectious Disease Control, The University of Texas Health Science Center at Tyler, Tyler, TX 75708, USA.
Kong
Ying
Y
Barnes
Peter F
PF
Huang
Fang-Fang
FF
Klucar
Peter
P
Wang
Xisheng
X
Samten
Buka
B
Sengupta
Mayami
M
Machona
Bruce
B
Donis
Ruben
R
Tvinnereim
Amy R
AR
Shams
Homayoun
H
D000818:Animals; D002478:Cells, Cultured; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D009980:Influenza A virus / Q000502:physiology*; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000166:cytology* / Q000187:drug effects / Q000382:microbiology; D051379:Mice; D008822:Mice, Transgenic; D009169:Mycobacterium tuberculosis / Q000502:physiology*; D009976:Orthomyxoviridae Infections / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics / Q000378:metabolism; D012906:Smoke / Q000009:adverse effects*; D013154:Spleen / Q000187:drug effects / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects*; D014026:Nicotiana; D014397:Tuberculosis, Pulmonary / Q000276:immunology
D011948:Receptors, Antigen, T-Cell; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D012906:Smoke; C105190:TNFRSF10A protein, human; D007371:Interferon-gamma