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

Juliane Lippmann, Stefan Rothenburg, Nikolaus Deigendesch, Julia Eitel, Karolin Meixenberger, Vincent Van Laak, Hortense Slevogt, Philippe Dje N'Guessan, Stefan Hippenstiel, Trinad Chakraborty, Antje Flieger, Norbert Suttorp, Bastian Opitz

Research output: Contribution to journalArticle

68 Scopus citations

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 IFNα/β 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 IFNβ, full-length hZBP1 and a prominent splice variant lacking the first Zα domain (hZBP1ΔZα) in human cells. Overexpression of hZBP1 but not hZBP1ΔZα slightly amplified poly(dA-dT)-stimulated IFNβ reporter activation in HEK293 cells, but had no effect on IFNβ and IL-8 production induced by bacteria or poly(dA-dT) in A549 cells. We found that mZBP1 siRNA impaired poly(dA-dT)-induced IFNβ responses in mouse L929 fibroblasts at a later time point, while multiple hZBP1 siRNAs did not suppress IFNβ or IL-8 expression induced by poly(dA-dT) or bacterial infection in human cells. In contrast, IRF3 siRNA strongly impaired the IFNβ responses to poly(dA-dT) or bacterial infection. In conclusion, intracellular bacteria and cytosolic poly(dA-dT) activate IFNβ responses in different human cells without requiring human ZBP1.

Original languageEnglish (US)
Pages (from-to)2579-2588
Number of pages10
JournalCellular Microbiology
Volume10
Issue number12
DOIs
StatePublished - 2008
Externally publishedYes

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Virology

Fingerprint Dive into the research topics of 'IFNβ responses induced by intracellular bacteria or cytosolic DNA in different human cells do not require ZBP1 (DLM-1/DAI)'. Together they form a unique fingerprint.

  • Cite this

    Lippmann, J., Rothenburg, S., Deigendesch, N., Eitel, J., Meixenberger, K., Van Laak, V., Slevogt, H., N'Guessan, P. D., Hippenstiel, S., Chakraborty, T., Flieger, A., Suttorp, N., & Opitz, B. (2008). IFNβ responses induced by intracellular bacteria or cytosolic DNA in different human cells do not require ZBP1 (DLM-1/DAI). Cellular Microbiology, 10(12), 2579-2588. https://doi.org/10.1111/j.1462-5822.2008.01232.x