The PYRIN Domain-only Protein POP3 Inhibits ALR Inflammasomes and Regulates Responses to Infection with DNA Viruses

Overview

Journal Nat Immunol

Date 2014 Feb 18

PMID 24531343

Citations 90

Authors

Sonal Khare

Rojo A Ratsimandresy

Lucia de Almeida

Carla M Cuda

Stephanie L Rellick

Alexander V Misharin

Melissa C Wallin

Anu Gangopadhyay

Eleonora Forte

Eva Gottwein

Harris Perlman

John C Reed

David R Greaves

Andrea Dorfleutner

Christian Stehlik

Affiliations

Soon will be listed here.

Abstract

The innate immune system responds to infection and tissue damage by activating cytosolic sensory complexes called 'inflammasomes'. Cytosolic DNA is sensed by AIM2-like receptors (ALRs) during bacterial and viral infections and in autoimmune diseases. Subsequently, recruitment of the inflammasome adaptor ASC links ALRs to the activation of caspase-1. A controlled immune response is crucial for maintaining homeostasis, but the regulation of ALR inflammasomes is poorly understood. Here we identified the PYRIN domain (PYD)-only protein POP3, which competes with ASC for recruitment to ALRs, as an inhibitor of DNA virus-induced activation of ALR inflammasomes in vivo. Data obtained with a mouse model with macrophage-specific POP3 expression emphasize the importance of the regulation of ALR inflammasomes in monocytes and macrophages.

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