AIM2-Like Receptors Positively and Negatively Regulate the Interferon Response Induced by Cytosolic DNA

ABSTRACT Cytosolic DNAs derived from retrotransposons serve as pathogen-associated molecular patterns for pattern recognition receptors (PRRs) that stimulate the induction of interferons (IFNs) and other cytokines, leading to autoimmune disease. Cyclic GMP-AMP synthase is one PRR that senses retrotr...

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Autores principales:	Yuki Nakaya, Jingtao Lilue, Spyridon Stavrou, Eileen A. Moran, Susan R. Ross
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2017
Materias:	ALR Aim2 Trex1 endogenous retrovirus retrotransposon self DNA Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/d254c4edf75e434e8607b6b4b3122261
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spelling	oai:doaj.org-article:d254c4edf75e434e8607b6b4b31222612021-11-15T15:51:43ZAIM2-Like Receptors Positively and Negatively Regulate the Interferon Response Induced by Cytosolic DNA10.1128/mBio.00944-172150-7511https://doaj.org/article/d254c4edf75e434e8607b6b4b31222612017-09-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00944-17https://doaj.org/toc/2150-7511ABSTRACT Cytosolic DNAs derived from retrotransposons serve as pathogen-associated molecular patterns for pattern recognition receptors (PRRs) that stimulate the induction of interferons (IFNs) and other cytokines, leading to autoimmune disease. Cyclic GMP-AMP synthase is one PRR that senses retrotransposon DNA, activating type I IFN responses through the stimulator of IFN genes (STING). Absent in melanoma 2 (AIM2)-like receptors (ALRs) have also been implicated in these pathways. Here we show that the mouse ALR IFI205 senses cytosolic retrotransposon DNA independently of cyclic GMP-AMP production. AIM2 antagonizes IFI205-mediated IFN induction activity by sequestering it from STING. We also found that the complement of genes located in the ALR locus in C57BL/6 and AIM2 knockout mice are different and unique, which has implications for interpretation of the sensing of pathogens in different mouse strains. Our data suggest that members of the ALR family are critical to the host IFN response to endogenous DNA. IMPORTANCE Autoimmune diseases like Aicardi-Goutières syndrome and lupus erythematosus arise when cells of the immune system become activated and attack host cells and tissues. We found that DNA generated by endogenous retroviruses and retroelements in inbred mice and mouse cells is recognized by several host proteins found in macrophages that are members of the ALR family and that these proteins both suppress and activate the pathways leading to the generation of cytokines and IFNs. We also show that there is great genetic diversity between different inbred mouse strains in the ALR genes, which might contribute to differential susceptibility to autoimmunity. Understanding how immune cells become activated is important to the control of disease.Yuki NakayaJingtao LilueSpyridon StavrouEileen A. MoranSusan R. RossAmerican Society for MicrobiologyarticleALRAim2Trex1endogenous retrovirusretrotransposonself DNAMicrobiologyQR1-502ENmBio, Vol 8, Iss 4 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	ALR Aim2 Trex1 endogenous retrovirus retrotransposon self DNA Microbiology QR1-502
spellingShingle	ALR Aim2 Trex1 endogenous retrovirus retrotransposon self DNA Microbiology QR1-502 Yuki Nakaya Jingtao Lilue Spyridon Stavrou Eileen A. Moran Susan R. Ross AIM2-Like Receptors Positively and Negatively Regulate the Interferon Response Induced by Cytosolic DNA
description	ABSTRACT Cytosolic DNAs derived from retrotransposons serve as pathogen-associated molecular patterns for pattern recognition receptors (PRRs) that stimulate the induction of interferons (IFNs) and other cytokines, leading to autoimmune disease. Cyclic GMP-AMP synthase is one PRR that senses retrotransposon DNA, activating type I IFN responses through the stimulator of IFN genes (STING). Absent in melanoma 2 (AIM2)-like receptors (ALRs) have also been implicated in these pathways. Here we show that the mouse ALR IFI205 senses cytosolic retrotransposon DNA independently of cyclic GMP-AMP production. AIM2 antagonizes IFI205-mediated IFN induction activity by sequestering it from STING. We also found that the complement of genes located in the ALR locus in C57BL/6 and AIM2 knockout mice are different and unique, which has implications for interpretation of the sensing of pathogens in different mouse strains. Our data suggest that members of the ALR family are critical to the host IFN response to endogenous DNA. IMPORTANCE Autoimmune diseases like Aicardi-Goutières syndrome and lupus erythematosus arise when cells of the immune system become activated and attack host cells and tissues. We found that DNA generated by endogenous retroviruses and retroelements in inbred mice and mouse cells is recognized by several host proteins found in macrophages that are members of the ALR family and that these proteins both suppress and activate the pathways leading to the generation of cytokines and IFNs. We also show that there is great genetic diversity between different inbred mouse strains in the ALR genes, which might contribute to differential susceptibility to autoimmunity. Understanding how immune cells become activated is important to the control of disease.
format	article
author	Yuki Nakaya Jingtao Lilue Spyridon Stavrou Eileen A. Moran Susan R. Ross
author_facet	Yuki Nakaya Jingtao Lilue Spyridon Stavrou Eileen A. Moran Susan R. Ross
author_sort	Yuki Nakaya
title	AIM2-Like Receptors Positively and Negatively Regulate the Interferon Response Induced by Cytosolic DNA
title_short	AIM2-Like Receptors Positively and Negatively Regulate the Interferon Response Induced by Cytosolic DNA
title_full	AIM2-Like Receptors Positively and Negatively Regulate the Interferon Response Induced by Cytosolic DNA
title_fullStr	AIM2-Like Receptors Positively and Negatively Regulate the Interferon Response Induced by Cytosolic DNA
title_full_unstemmed	AIM2-Like Receptors Positively and Negatively Regulate the Interferon Response Induced by Cytosolic DNA
title_sort	aim2-like receptors positively and negatively regulate the interferon response induced by cytosolic dna
publisher	American Society for Microbiology
publishDate	2017
url	https://doaj.org/article/d254c4edf75e434e8607b6b4b3122261
work_keys_str_mv	AT yukinakaya aim2likereceptorspositivelyandnegativelyregulatetheinterferonresponseinducedbycytosolicdna AT jingtaolilue aim2likereceptorspositivelyandnegativelyregulatetheinterferonresponseinducedbycytosolicdna AT spyridonstavrou aim2likereceptorspositivelyandnegativelyregulatetheinterferonresponseinducedbycytosolicdna AT eileenamoran aim2likereceptorspositivelyandnegativelyregulatetheinterferonresponseinducedbycytosolicdna AT susanrross aim2likereceptorspositivelyandnegativelyregulatetheinterferonresponseinducedbycytosolicdna
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AIM2-Like Receptors Positively and Negatively Regulate the Interferon Response Induced by Cytosolic DNA

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