Cigarette smoke suppresses TLR-7 stimulation in response to virus infection in plasmacytoid dendritic cells
Exposure to environmental tobacco smoke (ETS) is associated with an increase in the frequency and severity of respiratory infections, including bronchiolitis, a clinical syndrome of infancy caused by viruses such as respiratory syncytial virus (RSV). The mechanisms by which ETS increases the risk of viral respiratory infections are largely unknown. A major effector integrating early antiviral and immunostimulatory activities is interferon-α (IFN-α), which is highly produced by plasmacytoid dendritic cells (pDC). In this work, we determined the effect of cigarette smoke extract (CSE) on human pDC immunity in response to a respiratory viral infection. We found that CSE inhibited RSV-induced IFN-α in pDC as well as the release of IL-1β, IL-10 and CXCL10. However, the production of additional cytokines and chemokines such as IL-6, TNF-α, CCL2, CCL3, CCL5 and CXCL8 was not altered. Quantitative RT-PCR analysis indicated that CSE decreased the expression of toll-like receptor (TLR)-7 and interferon regulatory factor (IRF)-7 in RSV-infected pDC. Furthermore, determination of IRF-7 phosphorylation by flow cytometry showed that CSE prevented IRF-7 activation. These data provide evidence that cigarette smoke suppresses key pDC functions upon viral infection by a mechanism that involves downregulation of TLR7 expression and decreased activation of IRF-7.
Publication Source (Journal or Book title)
Toxicology in vitro : an international journal published in association with BIBRA
Castro, S. M., Chakraborty, K., & Guerrero-Plata, A. (2011). Cigarette smoke suppresses TLR-7 stimulation in response to virus infection in plasmacytoid dendritic cells. Toxicology in vitro : an international journal published in association with BIBRA, 25 (5), 1106-13. https://doi.org/10.1016/j.tiv.2011.03.011