TY - JOUR
T1 - 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
AU - Yang, Kun
AU - Puel, Anne
AU - Zhang, Shenying
AU - Eidenschenk, Céline
AU - Ku, Cheng-Lung
AU - Casrouge, Armanda
AU - Picard, Capucine
AU - von Bernuth, Horst
AU - Senechal, Brigitte
AU - Plancoulaine, Sabine
AU - Al-Hajjar, Sami
AU - Al-Ghonaium, Abdulaziz
AU - Maródi, László
AU - Davidson, Donald
AU - Speert, David
AU - Roifman, Chaim
AU - Garty, Ben-Zion
AU - Ozinsky, Adrian
AU - Barrat, Franck J
AU - Coffman, Robert L
AU - Miller, Richard L
AU - Li, Xiaoxia
AU - Lebon, Pierre
AU - Rodriguez-Gallego, Carlos
AU - Chapel, Helen
AU - Geissmann, Frédéric
AU - Jouanguy, Emmanuelle
AU - Casanova, Jean-Laurent
PY - 2005/11
Y1 - 2005/11
N2 - 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.
AB - 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.
KW - Fibroblasts
KW - Gene Expression Regulation
KW - Humans
KW - Interferons
KW - Interleukin-1 Receptor-Associated Kinases
KW - Phosphotransferases (Alcohol Group Acceptor)
KW - Poly I-C
KW - Signal Transduction
KW - Toll-Like Receptor 7
KW - Toll-Like Receptor 8
KW - Toll-Like Receptor 9
KW - Toll-Like Receptors
KW - Virus Diseases
KW - Viruses
U2 - 10.1016/j.immuni.2005.09.016
DO - 10.1016/j.immuni.2005.09.016
M3 - Article
C2 - 16286015
VL - 23
SP - 465
EP - 478
JO - Immunity
JF - Immunity
SN - 1074-7613
IS - 5
ER -