ABSTRACTSmoking 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 withMycobacterium tuberculosisby aerosol or influenza A by intranasal infection. Some mice were given a DNA vaccine encoding an immunogenicM. tuberculosisprotein. 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 stimulationin vitrowith anti-CD3, after vaccination with a construct expressing an immunogenic mycobacterial protein, and during infection withM. tuberculosisand influenza A virusin 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 withM. tuberculosisand 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 toM. tuberculosisand influenza virus in a physiologically relevant animal model, increasing susceptibility to both pathogens.
Development of a BALB/c 3T3 neutral red uptake cytotoxicity test using a mainstream cigarette smoke exposure system