IFNbeta responses induced by intracellular bacteria or cytosolic DNA in different human cells do not require ZBP1 (DLM-1/DAI) |
| |
Authors: | Lippmann Juliane Rothenburg Stefan Deigendesch Nikolaus Eitel Julia Meixenberger Karolin van Laak Vincent Slevogt Hortense N'guessan Philippe Dje Hippenstiel Stefan Chakraborty Trinad Flieger Antje Suttorp Norbert Opitz Bastian |
| |
Institution: | 1. Department of Internal Medicine/Infectious Diseases and Pulmonary Medicine, Charité Universit?tsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.;2. National Institutes of Health, National Institute of Child and Human Development, Bethesda, MD 20892‐2427, USA.;3. Institute of Immunology, University Hospital Hamburg‐Eppendorf, Hamburg, Germany.;4. Institute for Medical Microbiology, Justus‐Liebig University of Giessen, Frankfurter Strasse 107, 35392, Giessen, Germany.;5. Robert Koch‐Institute, Research Group NG5 Pathogenesis of Legionella Infections, Nordufer 20, 13353 Berlin, Germany. |
| |
Abstract: | Intracellular bacteria and cytosolic stimulation with DNA activate type I IFN responses independently of Toll-like receptors, most Nod-like receptors and RIG-like receptors. A recent study suggested that ZBP1 (DLM-1/DAI) represents the long anticipated pattern recognition receptor which mediates IFNalpha/beta responses to cytosolic DNA in mice. Here we show that Legionella pneumophila infection, and intracellular challenge with poly(dA-dT), but not with poly(dG-dC), induced expression of IFNbeta, full-length hZBP1 and a prominent splice variant lacking the first Zalpha domain (hZBP1DeltaZalpha) in human cells. Overexpression of hZBP1 but not hZBP1DeltaZalpha slightly amplified poly(dA-dT)-stimulated IFNbeta reporter activation in HEK293 cells, but had no effect on IFNbeta and IL-8 production induced by bacteria or poly(dA-dT) in A549 cells. We found that mZBP1 siRNA impaired poly(dA-dT)-induced IFNbeta responses in mouse L929 fibroblasts at a later time point, while multiple hZBP1 siRNAs did not suppress IFNbeta or IL-8 expression induced by poly(dA-dT) or bacterial infection in human cells. In contrast, IRF3 siRNA strongly impaired the IFNbeta responses to poly(dA-dT) or bacterial infection. In conclusion, intracellular bacteria and cytosolic poly(dA-dT) activate IFNbeta responses in different human cells without requiring human ZBP1. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|