|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
Ku, Cheng Lung
Von Bernuth, Horst
Garty, Ben Zion
Barrat, Franck J.
Coffman, Robert L.
Miller, Richard L.
Casanova, Jean Laurent
|UNESCO Clasification:||32 Ciencias médicas
3205 Medicina interna
|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)|
|Appears in Collections:||Artículos|
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