title: IFNbeta responses induced by intracellular bacteria or cytosolic DNA in different human cells do not require ZBP1 (DLM-1/DAI).
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.
authors.affiliation: Department of Internal Medicine/Infectious Diseases and Pulmonary Medicine, Charité Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.
authors.forename: Juliane
authors.initials: J
authors.lastname: Lippmann
authors.forename: Stefan
authors.initials: S
authors.lastname: Rothenburg
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Deigendesch
authors.forename: Julia
authors.initials: J
authors.lastname: Eitel
authors.forename: Karolin
authors.initials: K
authors.lastname: Meixenberger
authors.forename: Vincent
authors.initials: V
authors.lastname: van Laak
authors.forename: Hortense
authors.initials: H
authors.lastname: Slevogt
authors.forename: Philippe Dje
authors.initials: PD
authors.lastname: N'guessan
authors.forename: Stefan
authors.initials: S
authors.lastname: Hippenstiel
authors.forename: Trinad
authors.initials: T
authors.lastname: Chakraborty
authors.forename: Antje
authors.initials: A
authors.lastname: Flieger
authors.forename: Norbert
authors.initials: N
authors.lastname: Suttorp
authors.forename: Bastian
authors.initials: B
authors.lastname: Opitz
mesh_terms: D000818:Animals; D002460:Cell Line; D004269:DNA, Bacterial / Q000276:immunology*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006801:Humans; D016899:Interferon-beta / Q000096:biosynthesis*; D016209:Interleukin-8 / Q000096:biosynthesis; D016952:Legionella pneumophila / Q000276:immunology*; D051379:Mice; D016601:RNA-Binding Proteins
chemical_list: D004269:DNA, Bacterial; D004268:DNA-Binding Proteins; D016209:Interleukin-8; D016601:RNA-Binding Proteins; C485731:ZBP1 protein, human; D016899:Interferon-beta