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

被引：225

作者：

Yang, K

Puel, A

Zhang, SY

Eidenschenk, C

Ku, CL

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, BZ

Ozinsky, A

Barrat, FJ

Coffman, RL

Miller, RL

Li, XX

Lebon, P

Rodriguez-Gallego, C

Chapel, H

Geissmann, F

Jouanguy, E

Casanova, JL ^{[1
]}

机构：

[1] Univ Paris, INSERM, U550, Lab Human Genet Infect Dis,Necker Med Sch, F-75015 Paris, France

[2] Shanghai Jiao Tong Univ, Sch Med, Rui Jin Hosp, French Chinese Lab Genet Life Sci, Shanghai 200025, Peoples R China

[3] Necker Enfants Malades Hosp, F-75015 Paris, France

[4] Hop Necker Enfants Malad, INSERM Avenir, Lab Mononuclear Cell Biol, F-75015 Paris, France

[5] King Faisal Specialist Hosp & Res Ctr, Dept Pediat, Riyadh 11211, Saudi Arabia

[6] Res Ctr, Riyadh 11211, Saudi Arabia

[7] Univ Debrecen, Dept Infect & Pediat Immunol, H-4012 Debrecen, Hungary

[8] Univ Debrecen, Hlth Sci Ctr, H-4012 Debrecen, Hungary

[9] British Columbia Res Inst Child & Family, Div Infect & Immunol Dis, Vancouver, BC V5Z 4H4, Canada

[10] Hosp Sick Children, Dept Paediat, Div Immunol Allergy, Toronto, ON M5G 1X8, Canada

[11] Schneider Childrens Med Ctr Israel, Dept Pediat, IL-49202 Petah Tiqwa, Israel

[12] Inst Syst Biol, Seattle, WA 98103 USA

[13] Dynavax Technol, Berkeley, CA 94710 USA

[14] 3M Co, St Paul, MN 55144 USA

[15] Cleveland Clin Fdn, Dept Immunol, Cleveland, OH 44195 USA

[16] Univ Paris, St Vincent Paul Hosp, Dept Virol, F-75015 Paris, France

[17] Gran Canaria Dr Negrin Hosp, Dept Immunol, Las Palmas Gran Canaria 35020, Spain

[18] John Radcliffe Hosp, Dept Immunol, Oxford OX3 9DU, England

来源：

IMMUNITY | 2005年 / 23卷 / 05期

关键词：

D O I：

10.1016/j.immuni.2005.09.016

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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 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.

引用

页码：465 / 478

页数：14

共 66 条

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