IFNb responses induced by intracellular bacteria or cytosolic DNA in different human cells do not require ZBP1 (DLM-1-DAI)

• Published in: Cellular microbiology Vol. 10; no. 12; pp. 2579 - 2588
• Main 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
• Format: Journal Article
• Language: English
• Published: 01.12.2008
• Subjects: Legionella pneumophila
• ISSN: 1462-5814; 1462-5822
• DOI: 10.1111/j.1462-5822.2008.01232.x

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 IFNa-b 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 IFNb, full-length hZBP1 and a prominent splice variant lacking the first Za domain (hZBP1Za) in human cells. Overexpression of hZBP1 but not hZBP1Za slightly amplified poly(dA-dT)-stimulated IFNb reporter activation in HEK293 cells, but had no effect on IFNb and IL-8 production induced by bacteria or poly(dA-dT) in A549 cells. We found that mZBP1 siRNA impaired poly(dA-dT)-induced IFNb responses in mouse L929 fibroblasts at a later time point, while multiple hZBP1 siRNAs did not suppress IFNb or IL-8 expression induced by poly(dA-dT) or bacterial infection in human cells. In contrast, IRF3 siRNA strongly impaired the IFNb responses to poly(dA-dT) or bacterial infection. In conclusion, intracellular bacteria and cytosolic poly(dA-dT) activate IFNb responses in different human cells without requiring human ZBP1.