It takes two to tango: cigarette smoke partners with viruses to promote emphysema
Rubin M. Tuder, Jeong H. Yun
Rubin M. Tuder, Jeong H. Yun
Published July 24, 2008
Citation Information: J Clin Invest. 2008;118(8):2689-2693. https://doi.org/10.1172/JCI36536.
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Commentary

It takes two to tango: cigarette smoke partners with viruses to promote emphysema

Abstract

Viruses constitute a constant and renewed threat to humans. Not only do viruses cause disease directly due to their tissue tropism and pathogenicity, but they have also been linked to autoimmunity. In their study in this issue of the JCI, Kang et al. show that exposure to cigarette smoke induces alterations in the innate immune response to viral infection and that these changes hasten alveolar destruction characteristic of emphysema in mice (see the related beginning on page 2771). This study builds on evidence that patients with chronic obstructive pulmonary disease have clinical exacerbations associated with viral or bacterial infections, which lead to worsened lung function and increased mortality. This novel paradigm may aid related genetic, biomarker, and therapeutic developments and provides important insights into the pathogenesis of emphysematous lung destruction.

Authors

Rubin M. Tuder, Jeong H. Yun

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Figure 1

Synergistic interaction between cigarette smoke and RNA viruses in emphysema in mice.

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Synergistic interaction between cigarette smoke and RNA viruses in emphy...
The combination of exposure to cigarette smoke and RNA viruses leads to alveolar cell apoptosis involving type I epithelial, type II epithelial, and endothelial cells, and enhanced alveolar inflammation (with influx of neutrophils and macrophages). As shown by Kang et al. (5) in their study in this issue of the JCI, the process of alveolar destruction is set up via activation of the RLH adaptor protein MAVS, the cytokines IL-12, IL-18, and IFN-γ, and the phosphorylation of the kinase PKR (5). Furthermore, this process may course with an imbalance between matrix protease and antiproteases, favoring fragmentation of extracellular matrix proteins, including elastin. The cell signaling pathways triggered in alveolar epithelial cells infected by RNA viruses or synthetic dsRNA are represented in Figure 2.