XIAP Loss Triggers RIPK3- and Caspase-8-Driven IL-1β Activation and Cell Death as a Consequence of TLR-MyD88-Induced cIAP1-TRAF2 Degradation
X-linked Inhibitor of Apoptosis (XIAP) deficiency predisposes people to pathogen-associated hyperinflammation. Upon XIAP loss, Toll-like receptor (TLR) ligation triggers RIPK3-caspase-8-mediated IL-1β activation and death in myeloid cells. How XIAP suppresses these events remains unclear. Here, we s...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2017-07-01
|
| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S221112471730904X |
| _version_ | 1818130023556579328 |
|---|---|
| author | Kate E. Lawlor Rebecca Feltham Monica Yabal Stephanie A. Conos Kaiwen W. Chen Stephanie Ziehe Carina Graß Yifan Zhan Tan A. Nguyen Cathrine Hall Angelina J. Vince Simon M. Chatfield Damian B. D’Silva Kenneth C. Pang Kate Schroder John Silke David L. Vaux Philipp J. Jost James E. Vince |
| author_facet | Kate E. Lawlor Rebecca Feltham Monica Yabal Stephanie A. Conos Kaiwen W. Chen Stephanie Ziehe Carina Graß Yifan Zhan Tan A. Nguyen Cathrine Hall Angelina J. Vince Simon M. Chatfield Damian B. D’Silva Kenneth C. Pang Kate Schroder John Silke David L. Vaux Philipp J. Jost James E. Vince |
| author_sort | Kate E. Lawlor |
| collection | DOAJ |
| description | X-linked Inhibitor of Apoptosis (XIAP) deficiency predisposes people to pathogen-associated hyperinflammation. Upon XIAP loss, Toll-like receptor (TLR) ligation triggers RIPK3-caspase-8-mediated IL-1β activation and death in myeloid cells. How XIAP suppresses these events remains unclear. Here, we show that TLR-MyD88 causes the proteasomal degradation of the related IAP, cIAP1, and its adaptor, TRAF2, by inducing TNF and TNF Receptor 2 (TNFR2) signaling. Genetically, we define that myeloid-specific cIAP1 loss promotes TLR-induced RIPK3-caspase-8 and IL-1β activity in the absence of XIAP. Importantly, deletion of TNFR2 in XIAP-deficient cells limited TLR-MyD88-induced cIAP1-TRAF2 degradation, cell death, and IL-1β activation. In contrast to TLR-MyD88, TLR-TRIF-induced interferon (IFN)β inhibited cIAP1 loss and consequent cell death. These data reveal how, upon XIAP deficiency, a TLR-TNF-TNFR2 axis drives cIAP1-TRAF2 degradation to allow TLR or TNFR1 activation of RIPK3-caspase-8 and IL-1β. This mechanism may explain why XIAP-deficient patients can exhibit symptoms reminiscent of patients with activating inflammasome mutations. |
| first_indexed | 2024-12-11T07:58:27Z |
| format | Article |
| id | doaj.art-b2bf45d4cadc4d619c18b1853295fdda |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-11T07:58:27Z |
| publishDate | 2017-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-b2bf45d4cadc4d619c18b1853295fdda2022-12-22T01:15:11ZengElsevierCell Reports2211-12472017-07-0120366868210.1016/j.celrep.2017.06.073XIAP Loss Triggers RIPK3- and Caspase-8-Driven IL-1β Activation and Cell Death as a Consequence of TLR-MyD88-Induced cIAP1-TRAF2 DegradationKate E. Lawlor0Rebecca Feltham1Monica Yabal2Stephanie A. Conos3Kaiwen W. Chen4Stephanie Ziehe5Carina Graß6Yifan Zhan7Tan A. Nguyen8Cathrine Hall9Angelina J. Vince10Simon M. Chatfield11Damian B. D’Silva12Kenneth C. Pang13Kate Schroder14John Silke15David L. Vaux16Philipp J. Jost17James E. Vince18The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, AustraliaThe Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, AustraliaIII. Medical Department for Hematology and Oncology, Klinikum rechts der Isar, Technische Universität München, 81675 Munich, GermanyThe Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, AustraliaInstitute for Molecular Bioscience and Centre for Inflammation and Disease Research, The University of Queensland, St. Lucia, QLD 4072, AustraliaIII. Medical Department for Hematology and Oncology, Klinikum rechts der Isar, Technische Universität München, 81675 Munich, GermanyIII. Medical Department for Hematology and Oncology, Klinikum rechts der Isar, Technische Universität München, 81675 Munich, GermanyThe Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, AustraliaThe Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, AustraliaThe Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, AustraliaThe Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, AustraliaThe Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, AustraliaThe Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, AustraliaThe Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, AustraliaInstitute for Molecular Bioscience and Centre for Inflammation and Disease Research, The University of Queensland, St. Lucia, QLD 4072, AustraliaThe Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, AustraliaThe Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, AustraliaIII. Medical Department for Hematology and Oncology, Klinikum rechts der Isar, Technische Universität München, 81675 Munich, GermanyThe Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, AustraliaX-linked Inhibitor of Apoptosis (XIAP) deficiency predisposes people to pathogen-associated hyperinflammation. Upon XIAP loss, Toll-like receptor (TLR) ligation triggers RIPK3-caspase-8-mediated IL-1β activation and death in myeloid cells. How XIAP suppresses these events remains unclear. Here, we show that TLR-MyD88 causes the proteasomal degradation of the related IAP, cIAP1, and its adaptor, TRAF2, by inducing TNF and TNF Receptor 2 (TNFR2) signaling. Genetically, we define that myeloid-specific cIAP1 loss promotes TLR-induced RIPK3-caspase-8 and IL-1β activity in the absence of XIAP. Importantly, deletion of TNFR2 in XIAP-deficient cells limited TLR-MyD88-induced cIAP1-TRAF2 degradation, cell death, and IL-1β activation. In contrast to TLR-MyD88, TLR-TRIF-induced interferon (IFN)β inhibited cIAP1 loss and consequent cell death. These data reveal how, upon XIAP deficiency, a TLR-TNF-TNFR2 axis drives cIAP1-TRAF2 degradation to allow TLR or TNFR1 activation of RIPK3-caspase-8 and IL-1β. This mechanism may explain why XIAP-deficient patients can exhibit symptoms reminiscent of patients with activating inflammasome mutations.http://www.sciencedirect.com/science/article/pii/S221112471730904XToll-like receptorNLRP3RIPK3caspase-8TNFR2XIAPcIAP1necroptosisinterferonautoinflammatory disease |
| spellingShingle | Kate E. Lawlor Rebecca Feltham Monica Yabal Stephanie A. Conos Kaiwen W. Chen Stephanie Ziehe Carina Graß Yifan Zhan Tan A. Nguyen Cathrine Hall Angelina J. Vince Simon M. Chatfield Damian B. D’Silva Kenneth C. Pang Kate Schroder John Silke David L. Vaux Philipp J. Jost James E. Vince XIAP Loss Triggers RIPK3- and Caspase-8-Driven IL-1β Activation and Cell Death as a Consequence of TLR-MyD88-Induced cIAP1-TRAF2 Degradation Cell Reports Toll-like receptor NLRP3 RIPK3 caspase-8 TNFR2 XIAP cIAP1 necroptosis interferon autoinflammatory disease |
| title | XIAP Loss Triggers RIPK3- and Caspase-8-Driven IL-1β Activation and Cell Death as a Consequence of TLR-MyD88-Induced cIAP1-TRAF2 Degradation |
| title_full | XIAP Loss Triggers RIPK3- and Caspase-8-Driven IL-1β Activation and Cell Death as a Consequence of TLR-MyD88-Induced cIAP1-TRAF2 Degradation |
| title_fullStr | XIAP Loss Triggers RIPK3- and Caspase-8-Driven IL-1β Activation and Cell Death as a Consequence of TLR-MyD88-Induced cIAP1-TRAF2 Degradation |
| title_full_unstemmed | XIAP Loss Triggers RIPK3- and Caspase-8-Driven IL-1β Activation and Cell Death as a Consequence of TLR-MyD88-Induced cIAP1-TRAF2 Degradation |
| title_short | XIAP Loss Triggers RIPK3- and Caspase-8-Driven IL-1β Activation and Cell Death as a Consequence of TLR-MyD88-Induced cIAP1-TRAF2 Degradation |
| title_sort | xiap loss triggers ripk3 and caspase 8 driven il 1β activation and cell death as a consequence of tlr myd88 induced ciap1 traf2 degradation |
| topic | Toll-like receptor NLRP3 RIPK3 caspase-8 TNFR2 XIAP cIAP1 necroptosis interferon autoinflammatory disease |
| url | http://www.sciencedirect.com/science/article/pii/S221112471730904X |
| work_keys_str_mv | AT kateelawlor xiaplosstriggersripk3andcaspase8drivenil1bactivationandcelldeathasaconsequenceoftlrmyd88inducedciap1traf2degradation AT rebeccafeltham xiaplosstriggersripk3andcaspase8drivenil1bactivationandcelldeathasaconsequenceoftlrmyd88inducedciap1traf2degradation AT monicayabal xiaplosstriggersripk3andcaspase8drivenil1bactivationandcelldeathasaconsequenceoftlrmyd88inducedciap1traf2degradation AT stephanieaconos xiaplosstriggersripk3andcaspase8drivenil1bactivationandcelldeathasaconsequenceoftlrmyd88inducedciap1traf2degradation AT kaiwenwchen xiaplosstriggersripk3andcaspase8drivenil1bactivationandcelldeathasaconsequenceoftlrmyd88inducedciap1traf2degradation AT stephanieziehe xiaplosstriggersripk3andcaspase8drivenil1bactivationandcelldeathasaconsequenceoftlrmyd88inducedciap1traf2degradation AT carinagraß xiaplosstriggersripk3andcaspase8drivenil1bactivationandcelldeathasaconsequenceoftlrmyd88inducedciap1traf2degradation AT yifanzhan xiaplosstriggersripk3andcaspase8drivenil1bactivationandcelldeathasaconsequenceoftlrmyd88inducedciap1traf2degradation AT tananguyen xiaplosstriggersripk3andcaspase8drivenil1bactivationandcelldeathasaconsequenceoftlrmyd88inducedciap1traf2degradation AT cathrinehall xiaplosstriggersripk3andcaspase8drivenil1bactivationandcelldeathasaconsequenceoftlrmyd88inducedciap1traf2degradation AT angelinajvince xiaplosstriggersripk3andcaspase8drivenil1bactivationandcelldeathasaconsequenceoftlrmyd88inducedciap1traf2degradation AT simonmchatfield xiaplosstriggersripk3andcaspase8drivenil1bactivationandcelldeathasaconsequenceoftlrmyd88inducedciap1traf2degradation AT damianbdsilva xiaplosstriggersripk3andcaspase8drivenil1bactivationandcelldeathasaconsequenceoftlrmyd88inducedciap1traf2degradation AT kennethcpang xiaplosstriggersripk3andcaspase8drivenil1bactivationandcelldeathasaconsequenceoftlrmyd88inducedciap1traf2degradation AT kateschroder xiaplosstriggersripk3andcaspase8drivenil1bactivationandcelldeathasaconsequenceoftlrmyd88inducedciap1traf2degradation AT johnsilke xiaplosstriggersripk3andcaspase8drivenil1bactivationandcelldeathasaconsequenceoftlrmyd88inducedciap1traf2degradation AT davidlvaux xiaplosstriggersripk3andcaspase8drivenil1bactivationandcelldeathasaconsequenceoftlrmyd88inducedciap1traf2degradation AT philippjjost xiaplosstriggersripk3andcaspase8drivenil1bactivationandcelldeathasaconsequenceoftlrmyd88inducedciap1traf2degradation AT jamesevince xiaplosstriggersripk3andcaspase8drivenil1bactivationandcelldeathasaconsequenceoftlrmyd88inducedciap1traf2degradation |