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

doi:10.1038/ni.2829

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 journal › Article › peer-review

133 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 language	English (US)
Pages (from-to)	343-353
Number of pages	11
Journal	Nature Immunology
Volume	15
Issue number	4
DOIs	https://doi.org/10.1038/ni.2829
State	Published - Apr 2014

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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Khare, S., Ratsimandresy, R. A., De Almeida, L., Cuda, C. M., Rellick, S. L., Misharin, A. V., Wallin, M. C., Gangopadhyay, A., Forte, E., Gottwein, E., Perlman, H., Reed, J. C., Greaves, D. R., Dorfleutner, A., & Stehlik, C. (2014). The PYRIN domain-only protein POP3 inhibits ALR inflammasomes and regulates responses to infection with DNA viruses. Nature Immunology, 15(4), 343-353. https://doi.org/10.1038/ni.2829

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

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.",

author = "Sonal Khare and Ratsimandresy, {Rojo A.} and {De Almeida}, L{\'u}cia and Cuda, {Carla M.} and Rellick, {Stephanie L.} and Misharin, {Alexander V.} and Wallin, {Melissa C.} and Anu Gangopadhyay and Eleonora Forte and Eva Gottwein and Harris Perlman and Reed, {John C.} and Greaves, {David R.} and Andrea Dorfleutner and Christian Stehlik",

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Khare, S, Ratsimandresy, RA, De Almeida, L, Cuda, CM, Rellick, SL, Misharin, AV, Wallin, MC, Gangopadhyay, A, Forte, E, Gottwein, E , Perlman, H, Reed, JC, Greaves, DR, Dorfleutner, A & Stehlik, C 2014, 'The PYRIN domain-only protein POP3 inhibits ALR inflammasomes and regulates responses to infection with DNA viruses', Nature Immunology, vol. 15, no. 4, pp. 343-353. https://doi.org/10.1038/ni.2829

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AU - Cuda, Carla M.

AU - Rellick, Stephanie L.

AU - Misharin, Alexander V.

AU - Wallin, Melissa C.

AU - Gangopadhyay, Anu

AU - Forte, Eleonora

AU - Gottwein, Eva

AU - Perlman, Harris

AU - Reed, John C.

AU - Greaves, David R.

AU - Dorfleutner, Andrea

AU - Stehlik, Christian

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

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