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.
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...
| Principais autores: | , , , , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | Journal article |
| Idioma: | English |
| Publicado em: |
2005
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| _version_ | 1826289148248457216 |
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| author | Yang, K Puel, A Zhang, S Eidenschenk, C Ku, C 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 Ozinsky, A Barrat, F Coffman, R Miller, R Li, X Lebon, P Rodriguez-Gallego, C Chapel, H |
| author_facet | Yang, K Puel, A Zhang, S Eidenschenk, C Ku, C 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 Ozinsky, A Barrat, F Coffman, R Miller, R Li, X Lebon, P Rodriguez-Gallego, C Chapel, H |
| author_sort | Yang, K |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T02:24:29Z |
| format | Journal article |
| id | oxford-uuid:a51e5320-cca8-4ff2-92cb-ab6f86a38e5b |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T02:24:29Z |
| publishDate | 2005 |
| record_format | dspace |
| spelling | oxford-uuid:a51e5320-cca8-4ff2-92cb-ab6f86a38e5b2022-03-27T02:38:22ZHuman TLR-7-, -8-, and -9-mediated induction of IFN-alpha/beta and -lambda Is IRAK-4 dependent and redundant for protective immunity to viruses.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:a51e5320-cca8-4ff2-92cb-ab6f86a38e5bEnglishSymplectic Elements at Oxford2005Yang, KPuel, AZhang, SEidenschenk, CKu, CCasrouge, APicard, Cvon Bernuth, HSenechal, BPlancoulaine, SAl-Hajjar, SAl-Ghonaium, AMaródi, LDavidson, DSpeert, DRoifman, CGarty, BOzinsky, ABarrat, FCoffman, RMiller, RLi, XLebon, PRodriguez-Gallego, CChapel, HFive 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. |
| spellingShingle | Yang, K Puel, A Zhang, S Eidenschenk, C Ku, C 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 Ozinsky, A Barrat, F Coffman, R Miller, R Li, X Lebon, P Rodriguez-Gallego, C Chapel, H 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. |
| 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. |
| title_full | 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. |
| title_fullStr | 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. |
| title_full_unstemmed | 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. |
| title_short | 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. |
| title_sort | 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 |
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