Human TLR-7-, -8-, and -9-mediated induction of IFN-α/β and -λ 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 journalArticle

208 Citations (Scopus)

Abstract

Five TLRs are thought to play an important role in antiviral immunity, sensing viral products and inducing IFN-α/β and -λ. Surprisingly, patients with a defect of IRAK-4, a critical kinase downstream from TLRs, are resistant to common viruses. We show here that IFN-α/β and -λ induction via TLR-7, TLR-8, and TLR-9 was abolished in IRAK-4-deficient blood cells. In contrast, IFN-α/β and -λ were induced normally by TLR-3 and TLR-4 agonists. Moreover, IFN-β and -λ were normally induced by TLR-3 agonists and viruses in IRAK-4-deficient fibroblasts. We further show that IFN-α/β and -λ 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-α/β and -λ is strictly IRAK-4 dependent and paradoxically redundant for protective immunity to most viruses in humans.

Original languageEnglish
Pages (from-to)465-478
Number of pages14
JournalImmunity
Volume23
Issue number5
DOIs
Publication statusPublished - Nov 2005

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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    Yang, K., Puel, A., Zhang, S., Eidenschenk, C., Ku, C. L., Casrouge, A., Picard, C., Von Bernuth, H., Senechal, B., Plancoulaine, S., Al-Hajjar, S., Al-Ghonaium, A., Maródi, L., Davidson, D., Speert, D., Roifman, C., Garty, B. Z., Ozinsky, A., Barrat, F. J., ... Casanova, J. L. (2005). Human TLR-7-, -8-, and -9-mediated induction of IFN-α/β and -λ Is IRAK-4 dependent and redundant for protective immunity to viruses. Immunity, 23(5), 465-478. https://doi.org/10.1016/j.immuni.2005.09.016