TY - JOUR
T1 - IFNβ responses induced by intracellular bacteria or cytosolic DNA in different human cells do not require ZBP1 (DLM-1/DAI)
AU - Lippmann, Juliane
AU - Rothenburg, Stefan
AU - Deigendesch, Nikolaus
AU - Eitel, Julia
AU - Meixenberger, Karolin
AU - Van Laak, Vincent
AU - Slevogt, Hortense
AU - N'Guessan, Philippe Dje
AU - Hippenstiel, Stefan
AU - Chakraborty, Trinad
AU - Flieger, Antje
AU - Suttorp, Norbert
AU - Opitz, Bastian
PY - 2008
Y1 - 2008
N2 - 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.
AB - 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.
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U2 - 10.1111/j.1462-5822.2008.01232.x
DO - 10.1111/j.1462-5822.2008.01232.x
M3 - Article
C2 - 18771559
AN - SCOPUS:55749088259
VL - 10
SP - 2579
EP - 2588
JO - Cellular Microbiology
JF - Cellular Microbiology
SN - 1462-5814
IS - 12
ER -