RNA editing by ADAR1 regulates innate and antiviral immune functions in primary macrophages
Pujantell, Maria (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Riveira-Muñoz, Eva (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Badia, Roger (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Castellví, Marc (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
García Vidal, Edurne (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Sirera, Guillem (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Puig, Teresa (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Ramirez, Cristina (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Clotet Sala, Bonaventura (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Este, José (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Ballana, Ester (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Universitat Autònoma de Barcelona. Departament de Medicina

Date:	2017
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.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Published in:	Scientific reports, Vol. 7 (october 2017) , ISSN 2045-2322

DOI: 10.1038/s41598-017-13580-0
PMID: 29042669

14 p, 2.0 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
Review > Revisió càrregues automàtiques
Articles > Research articles
Articles > Published articles