Please use this identifier to cite or link to this item: http://hdl.handle.net/10553/48640
Title: 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
Authors: Yang, Kun
Puel, Anne
Zhang, Shenying
Eidenschenk, Céline
Ku, Cheng Lung
Casrouge, Armanda
Picard, Capucine
Von Bernuth, Horst
Senechal, Brigitte
Plancoulaine, Sabine
Al-Hajjar, Sami
Al-Ghonaium, Abdulaziz
Maródi, László
Davidson, Donald
Speert, David
Roifman, Chaim
Garty, Ben Zion
Ozinsky, Adrian
Barrat, Franck J.
Coffman, Robert L.
Miller, Richard L.
Li, Xiaoxia
Lebon, Pierre
Rodriguez-Gallego, Carlos 
Chapel, Helen
Geissmann, Frédéric
Jouanguy, Emmanuelle
Casanova, Jean Laurent
UNESCO Clasification: 32 Ciencias médicas
3205 Medicina interna
Keywords: Immunity
Viruses
Issue Date: 2005
Journal: Immunity 
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.
URI: http://hdl.handle.net/10553/48640
ISSN: 1074-7613
DOI: 10.1016/j.immuni.2005.09.016
Source: Immunity[ISSN 1074-7613],v. 23, p. 465-478 (Noviembre 2005)
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