IFNb responses induced by intracellular bacteria or cytosolic DNA in different human cells do not require ZBP1 (DLM-1-DAI)
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 IFN...
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Published in | Cellular microbiology Vol. 10; no. 12; pp. 2579 - 2588 |
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Main Authors | , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
01.12.2008
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Subjects | |
Online Access | Get full text |
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Summary: | 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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 content type line 23 ObjectType-Feature-2 |
ISSN: | 1462-5814 1462-5822 |
DOI: | 10.1111/j.1462-5822.2008.01232.x |