Human TLR-7-, -8-, and -9-mediated induction of IFN-alpha/beta and -lambda Is IRAK-4 dependent and redundant for protective immunity to viruses

Kun Yang, Anne Puel, Shenying Zhang, Céline Eidenschenk, Cheng-Lung Ku, Armanda Casrouge, Capucine Picard, Horst von Bernuth, Brigitte Senechal, Sabine Plancoulaine, Sami Al-Hajjar, Abdulaziz Al-Ghonaium, László Maródi, Donald Davidson, David Speert, Chaim Roifman, Ben-Zion Garty, Adrian Ozinsky, Franck J Barrat, Robert L CoffmanRichard L Miller, Xiaoxia Li, Pierre Lebon, Carlos Rodriguez-Gallego, Helen Chapel, Frédéric Geissmann, Emmanuelle Jouanguy, Jean-Laurent Casanova

Research output: Contribution to journalArticlepeer-review

Abstract

Five TLRs are thought to play an important role in antiviral immunity, sensing viral products and inducing IFN-alpha/beta and -lambda. Surprisingly, patients with a defect of IRAK-4, a critical kinase downstream from TLRs, are resistant to common viruses. We show here that IFN-alpha/beta and -lambda induction via TLR-7, TLR-8, and TLR-9 was abolished in IRAK-4-deficient blood cells. In contrast, IFN-alpha/beta and -lambda were induced normally by TLR-3 and TLR-4 agonists. Moreover, IFN-beta and -lambda were normally induced by TLR-3 agonists and viruses in IRAK-4-deficient fibroblasts. We further show that IFN-alpha/beta and -lambda production in response to 9 of 11 viruses tested was normal or weakly affected in IRAK-4-deficient blood cells. Thus, IRAK-4-deficient patients may control viral infections by TLR-3- and TLR-4-dependent and/or TLR-independent production of IFNs. The TLR-7-, TLR-8-, and TLR-9-dependent induction of IFN-alpha/beta and -lambda is strictly IRAK-4 dependent and paradoxically redundant for protective immunity to most viruses in humans.

Original languageEnglish
Pages (from-to)465-78
Number of pages14
JournalImmunity
Volume23
Issue number5
DOIs
Publication statusPublished - Nov 2005

Keywords

  • Fibroblasts
  • Gene Expression Regulation
  • Humans
  • Interferons
  • Interleukin-1 Receptor-Associated Kinases
  • Phosphotransferases (Alcohol Group Acceptor)
  • Poly I-C
  • Signal Transduction
  • Toll-Like Receptor 7
  • Toll-Like Receptor 8
  • Toll-Like Receptor 9
  • Toll-Like Receptors
  • Virus Diseases
  • Viruses

Fingerprint Dive into the research topics of 'Human TLR-7-, -8-, and -9-mediated induction of IFN-alpha/beta and -lambda Is IRAK-4 dependent and redundant for protective immunity to viruses'. Together they form a unique fingerprint.

Cite this