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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
Five TLRs are thought to play an important role in antiviral immunity, sensing viral products and inducing IFN-α/β and -λ. Surprisingly, patients with a defect of IRAK-4, a critical kinase downstream from TLRs, are resistant to common viruses. We show here that IFN-α/β and -λ induction via TLR-7, TL...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier Inc.
2005
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7111074/ https://www.ncbi.nlm.nih.gov/pubmed/16286015 http://dx.doi.org/10.1016/j.immuni.2005.09.016 |
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author | 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 |
author_facet | 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 |
author_sort | Yang, Kun |
collection | PubMed |
description | Five TLRs are thought to play an important role in antiviral immunity, sensing viral products and inducing IFN-α/β and -λ. Surprisingly, patients with a defect of IRAK-4, a critical kinase downstream from TLRs, are resistant to common viruses. We show here that IFN-α/β and -λ induction via TLR-7, TLR-8, and TLR-9 was abolished in IRAK-4-deficient blood cells. In contrast, IFN-α/β and -λ were induced normally by TLR-3 and TLR-4 agonists. Moreover, IFN-β and -λ were normally induced by TLR-3 agonists and viruses in IRAK-4-deficient fibroblasts. We further show that IFN-α/β and -λ 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-α/β and -λ is strictly IRAK-4 dependent and paradoxically redundant for protective immunity to most viruses in humans. |
format | Online Article Text |
id | pubmed-7111074 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2005 |
publisher | Elsevier Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-71110742020-04-02 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 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 Immunity Article Five TLRs are thought to play an important role in antiviral immunity, sensing viral products and inducing IFN-α/β and -λ. Surprisingly, patients with a defect of IRAK-4, a critical kinase downstream from TLRs, are resistant to common viruses. We show here that IFN-α/β and -λ induction via TLR-7, TLR-8, and TLR-9 was abolished in IRAK-4-deficient blood cells. In contrast, IFN-α/β and -λ were induced normally by TLR-3 and TLR-4 agonists. Moreover, IFN-β and -λ were normally induced by TLR-3 agonists and viruses in IRAK-4-deficient fibroblasts. We further show that IFN-α/β and -λ 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-α/β and -λ is strictly IRAK-4 dependent and paradoxically redundant for protective immunity to most viruses in humans. Elsevier Inc. 2005-11 2005-11-15 /pmc/articles/PMC7111074/ /pubmed/16286015 http://dx.doi.org/10.1016/j.immuni.2005.09.016 Text en Copyright © 2005 Elsevier Inc. All rights reserved. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. |
spellingShingle | Article 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-α/β and -λ Is IRAK-4 Dependent and Redundant for Protective Immunity to Viruses |
title | 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 |
title_full | 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 |
title_fullStr | 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 |
title_full_unstemmed | 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 |
title_short | 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 |
title_sort | 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 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7111074/ https://www.ncbi.nlm.nih.gov/pubmed/16286015 http://dx.doi.org/10.1016/j.immuni.2005.09.016 |
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