Yang et al (2005) Human TLR-7, -8 and -9-mediated induction of IFN-a/b is IRAK-4-dependent and redundant for protective immunity to viruses. Immunity 23; 465-478

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.

Yang, K., Puel, A., Eidenschenk, C., Zhang, S., Casrouge, A., Picard, C., Ku, C-L, von Bernuth, H., Senechal, B., Al-Hajjar, S., Al-Ghonaium, A., Chapel, H., Maródi, L., Davidson, D. J., Speert, D., Rodriguez-Gallego, C., Ozinsky, A., Barrat, F.J., Coffman, R. L., Miller, R. L., Li, X., Geissmann, F., Jouanguy, E., Casanova, J-L.
Immunity (2005) 23; 465-478    PubMed
Davidson supported by funding from: Wellcome Trust/ CCFF

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. PMID: 16286015
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