Journal article
The adaptor ASC has extracellular and 'prionoid' activities that propagate inflammation
BS Franklin, L Bossaller, D De Nardo, JM Ratter, A Stutz, G Engels, C Brenker, M Nordhoff, SR Mirandola, A Al-Amoudi, MS Mangan, S Zimmer, BG Monks, M Fricke, RE Schmidt, T Espevik, B Jones, AG Jarnicki, PM Hansbro, P Busto Show all
Nature Immunology | NATURE PUBLISHING GROUP | Published : 2014
DOI: 10.1038/ni.2913
Abstract
Microbes or danger signals trigger inflammasome sensors, which induce polymerization of the adaptor ASC and the assembly of ASC specks. ASC specks recruit and activate caspase-1, which induces maturation of the cytokine interleukin 1β (IL-1β) and pyroptotic cell death. Here we found that after pyroptosis, ASC specks accumulated in the extracellular space, where they promoted further maturation of IL-1β. In addition, phagocytosis of ASC specks by macrophages induced lysosomal damage and nucleation of soluble ASC, as well as activation of IL-1β in recipient cells. ASC specks appeared in bodily fluids from inflamed tissues, and autoantibodies to ASC specks developed in patients and mice with au..
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Awarded by National Institutes of Health
Funding Acknowledgements
We thank C. Tiberi and P.-I. Chiang for technical support. Supported by Deutsche Forschungsgemeinschaft (SFB670 to E.L.), the US National Institutes of Health (R01-HL093262, R01-HL112661 and R01-AI083713 to E.L.), the Alexander von Humboldt Foundation (B.S.F.), intramural BONFOR research support at the University of Bonn (B.S.F.), the European Research Council (Advanced Grant to A.A.), the European Union (NEURINOX to A.A.), the Swiss National Foundation (Sinergia grant to A.A.), the Novartis Research Foundation (A.A.), the Clinical Research Priority Programs "Small RNAs" and "Mechanisms of Human Hemato-Lymphatic Diseases" of the University of Zurich (A.A.), the ImmunoSensation cluster of Excellence in Bonn (E.L.) and the German Center for Infection Research (E.L.).