IPS-1 signaling has a nonredundant role in mediating antiviral responses and the clearance of respiratory syncytial virus
The cytosolic RNA helicases melanoma differentiation-associated gene 5 and retinoic acid-inducible gene-I and their adaptor IFN-β promoter stimulator (IPS-1) have been implicated in the recognition of viral RNA and the production of type I IFN. Complementing the endosomal TLR, melanoma differentiation-associated gene 5, and retinoic acid-inducible gene-I provides alternative mechanisms for viral detection in cells with reduced phagocytosis or autophagy. The infection route of respiratory syncytial virus (RSV)-via fusion of virus particles with the cell membrane-points to IPS-1 signaling as the pathway of choice for downstream antiviral responses. In the current study, viral clearance and inflammation resolution were indeed strongly affected by the absence of an initial IPS-1-mediated IFN-β response. Despite the blunted inflammatory response in IPS-1-deficient alveolar epithelial cells, pulmonary macrophages, and CD11b(+) dendritic cells (DC), the lungs of RSV-infected IPS-1-knockout mice showed augmented recruitment of inflammatory neutrophils, monocytes, and DC. Interestingly, pulmonary CD103(+) DC could functionally compensate for IPS-1 deficiency with the upregulation of certain inflammatory cytokines and chemokines, possibly via TLR3 and TLR7 signaling. The increased inflammation and reduced viral clearance in IPS-1-knockout mice was accompanied by increased T cell activation and IFN-γ production. Experiments with bone marrow chimeras indicated that RSV-induced lung pathology was most severe when IPS-1 expression was lacking in both immune and nonimmune cell populations. Similarly, viral clearance was rescued upon restored IPS-1 signaling in either the nonimmune or the immune compartment. These data support a nonredundant function for IPS-1 in controlling RSV-induced inflammation and viral replication.
Medienart: |
E-Artikel |
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Erscheinungsjahr: |
2012 |
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Erschienen: |
2012 |
Enthalten in: |
Zur Gesamtaufnahme - volume:189 |
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Enthalten in: |
Journal of immunology (Baltimore, Md. : 1950) - 189(2012), 12 vom: 15. Dez., Seite 5942-53 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Demoor, Tine [VerfasserIn] |
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Links: |
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Themen: |
Adaptor Proteins, Signal Transducing |
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Anmerkungen: |
Date Completed 21.02.2013 Date Revised 21.10.2021 published: Print-Electronic Citation Status MEDLINE |
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doi: |
10.4049/jimmunol.1201763 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM222469854 |
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520 | |a The cytosolic RNA helicases melanoma differentiation-associated gene 5 and retinoic acid-inducible gene-I and their adaptor IFN-β promoter stimulator (IPS-1) have been implicated in the recognition of viral RNA and the production of type I IFN. Complementing the endosomal TLR, melanoma differentiation-associated gene 5, and retinoic acid-inducible gene-I provides alternative mechanisms for viral detection in cells with reduced phagocytosis or autophagy. The infection route of respiratory syncytial virus (RSV)-via fusion of virus particles with the cell membrane-points to IPS-1 signaling as the pathway of choice for downstream antiviral responses. In the current study, viral clearance and inflammation resolution were indeed strongly affected by the absence of an initial IPS-1-mediated IFN-β response. Despite the blunted inflammatory response in IPS-1-deficient alveolar epithelial cells, pulmonary macrophages, and CD11b(+) dendritic cells (DC), the lungs of RSV-infected IPS-1-knockout mice showed augmented recruitment of inflammatory neutrophils, monocytes, and DC. Interestingly, pulmonary CD103(+) DC could functionally compensate for IPS-1 deficiency with the upregulation of certain inflammatory cytokines and chemokines, possibly via TLR3 and TLR7 signaling. The increased inflammation and reduced viral clearance in IPS-1-knockout mice was accompanied by increased T cell activation and IFN-γ production. Experiments with bone marrow chimeras indicated that RSV-induced lung pathology was most severe when IPS-1 expression was lacking in both immune and nonimmune cell populations. Similarly, viral clearance was rescued upon restored IPS-1 signaling in either the nonimmune or the immune compartment. These data support a nonredundant function for IPS-1 in controlling RSV-induced inflammation and viral replication | ||
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700 | 1 | |a Petersen, Bryan C |e verfasserin |4 aut | |
700 | 1 | |a Morris, Susan |e verfasserin |4 aut | |
700 | 1 | |a Mukherjee, Sumanta |e verfasserin |4 aut | |
700 | 1 | |a Ptaschinski, Catherine |e verfasserin |4 aut | |
700 | 1 | |a De Almeida Nagata, Denise E |e verfasserin |4 aut | |
700 | 1 | |a Kawai, Taro |e verfasserin |4 aut | |
700 | 1 | |a Ito, Toshihiro |e verfasserin |4 aut | |
700 | 1 | |a Akira, Shizuo |e verfasserin |4 aut | |
700 | 1 | |a Kunkel, Steven L |e verfasserin |4 aut | |
700 | 1 | |a Schaller, Matthew A |e verfasserin |4 aut | |
700 | 1 | |a Lukacs, Nicholas W |e verfasserin |4 aut | |
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