RAIDD Mediates TLR3 and IRF7 Driven Type i Interferon Production

Sathish Kumar Maney, Haifeng C. Xu, Jun Huang, Aleksandra A. Pandyra, Christian Ehlting, Renan Aguilar-Valenzuela, Vitaly I. Pozdeev, David R. McIlwain, Albert Zimmermann, Johannes G. Bode, Hartmut Hengel, Carsten J. Kirschning, Ira R. Kim, John Hiscott, Dirk Brenner, Dieter Häussinger, Pamela S. Ohashi, Tak W. Mak, Karl S. Lang, Philipp A. Lang*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

3 Citations (Scopus)

Abstract

Background/Aims: Viral infections represent a global health problem with the need for new viral therapies and better understanding of the immune response during infection. The most immediate and potent anti-viral defense mechanism is the production of type I interferon (IFN-I) which are activated rapidly following recognition of viral infection by host pathogen recognition receptors (PRR). The mechanisms of innate cellular signaling downstream of PRR activation remain to be fully understood. In the present study, we demonstrate that CASP2 and RIPK1 domain-containing adaptor with death domain (CRADD/RAIDD) is a critical component in type I IFN production. Methods: The role of RAIDD during IFN-I production was investigated using western blot, shRNA mediated lentiviral knockdown, immunoprecipitation and IFN-I driven dual luciferase assay. Results: Immunoprecipitation analysis revealed the molecular interaction of RAIDD with interferon regulatory factor 7 (IRF7) and its phosphorylating kinase IKKϵ. Using an IFN-4α driven dual luciferase analysis in RAIDD deficient cells, type I IFN activation by IKKϵ and IRF7 was dramatically reduced. Furthermore, deletion of either the caspase recruitment domain (CARD) or death domain (DD) of RAIDD inhibited IKKϵ and IRF7 mediated interferon-4α activation. Conclusion: We have identified that the adaptor molecule RAIDD coordinates IKKϵ and IRF7 interaction to ensure efficient expression of type I interferon.

Original languageEnglish
Pages (from-to)1271-1280
Number of pages10
JournalCellular Physiology and Biochemistry
Volume39
Issue number4
DOIs
Publication statusPublished - 1 Sep 2016

Keywords

  • Innate immunity
  • IRF7
  • RAIDD
  • TLR

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