The PYRIN domain-only protein POP3 inhibits ALR inflammasomes and regulates responses to infection with DNA viruses

Sonal Khare, Rojo A. Ratsimandresy, Lúcia 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

*Corresponding author for this work

Research output: Contribution to journalArticle

82 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)343-353
Number of pages11
JournalNature Immunology
Volume15
Issue number4
DOIs
StatePublished - Apr 2014

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'The PYRIN domain-only protein POP3 inhibits ALR inflammasomes and regulates responses to infection with DNA viruses'. Together they form a unique fingerprint.

  • Cite this