title: Cigarette smoke suppresses TLR-7 stimulation in response to virus infection in plasmacytoid dendritic cells.
abstract: 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.
authors: Department of Pathobiological Sciences, Louisiana State University, Baton Rouge, LA 70803, USA.
authors: Shawn M
authors: SM
authors: Castro
authors: Krishnendu
authors: K
authors: Chakraborty
authors: Antonieta
authors: A
authors: Guerrero-Plata
mesh_terms: D002478:Cells, Cultured; D054357:Chemokine CXCL10 / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects* / Q000821:virology*; D015536:Down-Regulation; D006801:Humans; D050839:Interferon Regulatory Factor-7 / Q000235:genetics / Q000378:metabolism; D016898:Interferon-alpha / Q000096:biosynthesis / Q000276:immunology; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000276:immunology; D010766:Phosphorylation; D012136:Respiratory Syncytial Viruses / Q000472:pathogenicity; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012906:Smoke / Q000009:adverse effects*; D051199:Toll-Like Receptor 7 / Q000235:genetics / Q000378:metabolism*
chemical_list: C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; C494234:IRF7 protein, human; D050839:Interferon Regulatory Factor-7; D016898:Interferon-alpha; D053583:Interleukin-1beta; D012906:Smoke; C495348:TLR7 protein, human; D051199:Toll-Like Receptor 7; D016753:Interleukin-10