Poly IC Triggers a Cathepsin D- and IPS-1-Dependent Pathway to Enhance Cytokine Production and Mediate Dendritic Cell Necroptosis
| Autor: | Hiroki Tanaka, Shizuo Akira, Kyung-Sue Shin, Tetsuo Tsuchida, Tatsuya Kozaki, Jian Zou, Himanshu Kumar, Taro Kawai |
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| Rok vydání: | 2013 |
| Předmět: |
Necroptosis
Immunology Cathepsin D Mice Inbred Strains Biology Caspase 8 Immunomodulation Mice Necrosis Animals Immunology and Allergy HMGB1 Protein Transcription factor Cells Cultured Adaptor Proteins Signal Transducing Mice Knockout Cathepsin GTPase-Activating Proteins Signal transducing adaptor protein Dendritic Cells Dendritic cell Immunity Innate Cell biology Mice Inbred C57BL Poly I-C Infectious Diseases Cytokines Signal transduction Protein Binding Signal Transduction |
| Zdroj: | Immunity. 38:717-728 |
| ISSN: | 1074-7613 |
| DOI: | 10.1016/j.immuni.2012.12.007 |
| Popis: | SummaryRIG-I-like receptors (RLRs) sense virus-derived RNA or polyinosinic-polycytidylic acid (poly IC) to exert antiviral immune responses. Here, we examine the mechanisms underlying the adjuvant effects of poly IC. Poly IC was taken up by dendritic cells (DCs), and it induced lysosomal destabilization, which, in turn, activated an RLR-dependent signaling pathway. Upon poly IC stimulation, cathepsin D was released into the cytoplasm from the lysosome to interact with IPS-1, an adaptor molecule for RLRs. This interaction facilitated cathepsin D cleavage of caspase 8 and the activation of the transcription factor NF-κB, resulting in enhanced cytokine production. Further recruitment of the kinase RIP-1 to this complex initiated the necroptosis of a small number of DCs. HMGB1 released by dying cells enhanced IFN-β production in concert with poly IC. Collectively, these findings suggest that cathepsin D-triggered, IPS-1-dependent necroptosis is a mechanism that propagates the adjuvant efficacy of poly IC. |
| Databáze: | OpenAIRE |
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