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

Sonal Khare, Rojo Anthony Ratsimandresy, Lucia Maria V De Almeida, Carla Marie Cuda, Stephanie L. Rellick, Alexander Misharin, Melissa C. Wallin, Anu Gangopadhyay, Eleonora Forte, Eva Gottwein, Harris R Perlman, John C. Reed, David R. Greaves, Andrea Dorfleutner*, Christian Stehlik

*Corresponding author for this work

Research output: Contribution to journalArticle

74 Citations (Scopus)

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 - Jan 1 2014

Fingerprint

DNA Virus Infections
Inflammasomes
Macrophages
Virus Activation
Caspase 1
DNA Viruses
Virus Diseases
Bacterial Infections
Autoimmune Diseases
Monocytes
Immune System
Homeostasis
Protein Domains
DNA
Infection

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Khare, Sonal ; Ratsimandresy, Rojo Anthony ; De Almeida, Lucia Maria V ; Cuda, Carla Marie ; Rellick, Stephanie L. ; Misharin, Alexander ; Wallin, Melissa C. ; Gangopadhyay, Anu ; Forte, Eleonora ; Gottwein, Eva ; Perlman, Harris R ; Reed, John C. ; Greaves, David R. ; Dorfleutner, Andrea ; Stehlik, Christian. / The PYRIN domain-only protein POP3 inhibits ALR inflammasomes and regulates responses to infection with DNA viruses. In: Nature Immunology. 2014 ; Vol. 15, No. 4. pp. 343-353.
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The PYRIN domain-only protein POP3 inhibits ALR inflammasomes and regulates responses to infection with DNA viruses. / Khare, Sonal; Ratsimandresy, Rojo Anthony; De Almeida, Lucia Maria V; Cuda, Carla Marie; Rellick, Stephanie L.; Misharin, Alexander; Wallin, Melissa C.; Gangopadhyay, Anu; Forte, Eleonora; Gottwein, Eva; Perlman, Harris R; Reed, John C.; Greaves, David R.; Dorfleutner, Andrea; Stehlik, Christian.

In: Nature Immunology, Vol. 15, No. 4, 01.01.2014, p. 343-353.

Research output: Contribution to journalArticle

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