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

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 Coffman; Richard L Miller; Xiaoxia Li; Pierre Lebon; Carlos Rodriguez-Gallego; Helen Chapel; Frédéric Geissmann; Emmanuelle Jouanguy; Jean-Laurent Casanova

doi:10.1016/j.immuni.2005.09.016

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

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 journal › Article › peer-review

Abstract

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.

Original language	English
Pages (from-to)	465-78
Number of pages	14
Journal	Immunity
Volume	23
Issue number	5
DOIs	https://doi.org/10.1016/j.immuni.2005.09.016
Publication status	Published - Nov 2005

Keywords

Fibroblasts
Gene Expression Regulation
Humans
Interferons
Interleukin-1 Receptor-Associated Kinases
Phosphotransferases (Alcohol Group Acceptor)
Poly I-C
Signal Transduction
Toll-Like Receptor 7
Toll-Like Receptor 8
Toll-Like Receptor 9
Toll-Like Receptors
Virus Diseases
Viruses

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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-alpha/beta and -lambda Is IRAK-4 dependent and redundant for protective immunity to viruses. Immunity, 23(5), 465-78. https://doi.org/10.1016/j.immuni.2005.09.016

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. / 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. In: Immunity. 2005 ; Vol. 23, No. 5. pp. 465-78.

@article{8ec773a7b022491c8e556cca4e49ca01,

title = "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",

abstract = "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.",

keywords = "Fibroblasts, Gene Expression Regulation, Humans, Interferons, Interleukin-1 Receptor-Associated Kinases, Phosphotransferases (Alcohol Group Acceptor), Poly I-C, Signal Transduction, Toll-Like Receptor 7, Toll-Like Receptor 8, Toll-Like Receptor 9, Toll-Like Receptors, Virus Diseases, Viruses",

author = "Kun Yang and Anne Puel and Shenying Zhang and C{\'e}line Eidenschenk and Cheng-Lung Ku and Armanda Casrouge and Capucine Picard and {von Bernuth}, Horst and Brigitte Senechal and Sabine Plancoulaine and Sami Al-Hajjar and Abdulaziz Al-Ghonaium and L{\'a}szl{\'o} Mar{\'o}di and Donald Davidson and David Speert and Chaim Roifman and Ben-Zion Garty and Adrian Ozinsky and Barrat, {Franck J} and Coffman, {Robert L} and Miller, {Richard L} and Xiaoxia Li and Pierre Lebon and Carlos Rodriguez-Gallego and Helen Chapel and Fr{\'e}d{\'e}ric Geissmann and Emmanuelle Jouanguy and Jean-Laurent Casanova",

year = "2005",

month = nov,

doi = "10.1016/j.immuni.2005.09.016",

language = "English",

volume = "23",

pages = "465--78",

journal = "Immunity",

issn = "1074-7613",

publisher = "Cell Press",

number = "5",

}

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, FJ, Coffman, RL, Miller, RL, Li, X, Lebon, P, Rodriguez-Gallego, C, Chapel, H, Geissmann, F, Jouanguy, E & Casanova, J-L 2005, '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', Immunity, vol. 23, no. 5, pp. 465-78. https://doi.org/10.1016/j.immuni.2005.09.016

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, 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.

In: Immunity, Vol. 23, No. 5, 11.2005, p. 465-78.

Research output: Contribution to journal › Article › peer-review

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 -