The Adaptor ASC Has Extracellular and 'prionoid' Activities That Propagate Inflammation

Overview

Journal Nat Immunol

Date 2014 Jun 23

PMID 24952505

Citations 422

Authors

Bernardo S Franklin

Lukas Bossaller

Dominic De Nardo

Jacqueline M Ratter

Andrea Stutz

Gudrun Engels

Christoph Brenker

Mark Nordhoff

Sandra R Mirandola

Ashraf Al-Amoudi

Matthew S Mangan

Sebastian Zimmer

Brian G Monks

Martin Fricke

Reinhold E Schmidt

Terje Espevik

Bernadette Jones

Andrew G Jarnicki

Philip M Hansbro

Patricia Busto

Ann Marshak-Rothstein

Simone Hornemann

Adriano Aguzzi

Wolfgang Kastenmuller

Eicke Latz

Affiliations

Soon will be listed here.

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 autoimmune pathologies. Together these findings reveal extracellular functions of ASC specks and a previously unknown form of cell-to-cell communication.

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