RNA editing by ADAR1 regulates innate and antiviral immune functions in primary macrophages

Abstract ADAR1-dependent A-to-I editing has recently been recognized as a key process for marking dsRNA as self, therefore, preventing innate immune activation and affecting the development and resolution of immune-mediated diseases and infections. Here, we have determined the role of ADAR1 as a reg...

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Autores principales:	Maria Pujantell, Eva Riveira-Muñoz, Roger Badia, Marc Castellví, Edurne Garcia-Vidal, Guillem Sirera, Teresa Puig, Cristina Ramirez, Bonaventura Clotet, José A. Esté, Ester Ballana
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b5349f651b58471ab2d3235a717d05d0
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spelling	oai:doaj.org-article:b5349f651b58471ab2d3235a717d05d02021-12-02T15:04:51ZRNA editing by ADAR1 regulates innate and antiviral immune functions in primary macrophages10.1038/s41598-017-13580-02045-2322https://doaj.org/article/b5349f651b58471ab2d3235a717d05d02017-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-13580-0https://doaj.org/toc/2045-2322Abstract ADAR1-dependent A-to-I editing has recently been recognized as a key process for marking dsRNA as self, therefore, preventing innate immune activation and affecting the development and resolution of immune-mediated diseases and infections. Here, we have determined the role of ADAR1 as a regulator of innate immune activation and modifier of viral susceptibility in primary myeloid and lymphoid cells. We show that ADAR1 knockdown significantly enhanced interferon, cytokine and chemokine production in primary macrophages that function as antiviral paracrine factors, rendering them resistant to HIV-1 infection. ADAR1 knockdown induced deregulation of the RLRs-MAVS signaling pathway, by increasing MDA5, RIG-I, IRF7 and phospho-STAT1 expression, an effect that was partially rescued by pharmacological blockade of the pathway. In summary, our results demonstrate a role of ADAR1 in regulating innate immune function in primary macrophages, suggesting that macrophages may play an essential role in disease associated to ADAR1 dysfunction. We also show that viral inhibition is exclusively dependent on innate immune activation consequence of ADAR1 knockdown, pointing towards ADAR1 as a potential target to boost antiviral immune response.Maria PujantellEva Riveira-MuñozRoger BadiaMarc CastellvíEdurne Garcia-VidalGuillem SireraTeresa PuigCristina RamirezBonaventura ClotetJosé A. EstéEster BallanaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Maria Pujantell Eva Riveira-Muñoz Roger Badia Marc Castellví Edurne Garcia-Vidal Guillem Sirera Teresa Puig Cristina Ramirez Bonaventura Clotet José A. Esté Ester Ballana RNA editing by ADAR1 regulates innate and antiviral immune functions in primary macrophages
description	Abstract ADAR1-dependent A-to-I editing has recently been recognized as a key process for marking dsRNA as self, therefore, preventing innate immune activation and affecting the development and resolution of immune-mediated diseases and infections. Here, we have determined the role of ADAR1 as a regulator of innate immune activation and modifier of viral susceptibility in primary myeloid and lymphoid cells. We show that ADAR1 knockdown significantly enhanced interferon, cytokine and chemokine production in primary macrophages that function as antiviral paracrine factors, rendering them resistant to HIV-1 infection. ADAR1 knockdown induced deregulation of the RLRs-MAVS signaling pathway, by increasing MDA5, RIG-I, IRF7 and phospho-STAT1 expression, an effect that was partially rescued by pharmacological blockade of the pathway. In summary, our results demonstrate a role of ADAR1 in regulating innate immune function in primary macrophages, suggesting that macrophages may play an essential role in disease associated to ADAR1 dysfunction. We also show that viral inhibition is exclusively dependent on innate immune activation consequence of ADAR1 knockdown, pointing towards ADAR1 as a potential target to boost antiviral immune response.
format	article
author	Maria Pujantell Eva Riveira-Muñoz Roger Badia Marc Castellví Edurne Garcia-Vidal Guillem Sirera Teresa Puig Cristina Ramirez Bonaventura Clotet José A. Esté Ester Ballana
author_facet	Maria Pujantell Eva Riveira-Muñoz Roger Badia Marc Castellví Edurne Garcia-Vidal Guillem Sirera Teresa Puig Cristina Ramirez Bonaventura Clotet José A. Esté Ester Ballana
author_sort	Maria Pujantell
title	RNA editing by ADAR1 regulates innate and antiviral immune functions in primary macrophages
title_short	RNA editing by ADAR1 regulates innate and antiviral immune functions in primary macrophages
title_full	RNA editing by ADAR1 regulates innate and antiviral immune functions in primary macrophages
title_fullStr	RNA editing by ADAR1 regulates innate and antiviral immune functions in primary macrophages
title_full_unstemmed	RNA editing by ADAR1 regulates innate and antiviral immune functions in primary macrophages
title_sort	rna editing by adar1 regulates innate and antiviral immune functions in primary macrophages
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/b5349f651b58471ab2d3235a717d05d0
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RNA editing by ADAR1 regulates innate and antiviral immune functions in primary macrophages

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