The Absence of Interferon-β Promotor Stimulator-1 (IPS-1) Predisposes to Bronchiolitis and Asthma-like Pathology in Response to Pneumoviral Infection in Mice

Abstract Respiratory syncytial virus (RSV)-bronchiolitis is a major cause of infant morbidity and mortality and a risk factor for subsequent asthma. We showed previously that toll-like receptor (TLR)7 in plasmacytoid dendritic cells (pDCs) is critical for protection against bronchiolitis and asthma...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Jennifer Simpson, Jason P. Lynch, Zhixuan Loh, Vivian Zhang, Rhiannon B. Werder, Kirsten Spann, Simon Phipps
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/16320a97d87d463db6bea7ee5c251f82
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:16320a97d87d463db6bea7ee5c251f82
record_format	dspace
spelling	oai:doaj.org-article:16320a97d87d463db6bea7ee5c251f822021-12-02T12:32:42ZThe Absence of Interferon-β Promotor Stimulator-1 (IPS-1) Predisposes to Bronchiolitis and Asthma-like Pathology in Response to Pneumoviral Infection in Mice10.1038/s41598-017-02564-92045-2322https://doaj.org/article/16320a97d87d463db6bea7ee5c251f822017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02564-9https://doaj.org/toc/2045-2322Abstract Respiratory syncytial virus (RSV)-bronchiolitis is a major cause of infant morbidity and mortality and a risk factor for subsequent asthma. We showed previously that toll-like receptor (TLR)7 in plasmacytoid dendritic cells (pDCs) is critical for protection against bronchiolitis and asthma in mice infected with pneumonia virus of mice (PVM), the mouse homolog of RSV. This lack of redundancy was unexpected as interferon-β promotor stimulator-1 (IPS-1) signalling, downstream of RIG-I-like receptor (RLR) and not TLR7 activation, contributes to host defence in hRSV-inoculated adult mice. To further clarify the role of IPS-1 signalling, we inoculated IPS-1−/− and WT mice with PVM in early-life, and again in later-life, to model the association between bronchiolitis and asthma. IPS-1 deficiency predisposed to severe PVM bronchiolitis, characterised by neutrophilic inflammation and necroptotic airway epithelial cell death, high mobility group box 1 (HMGB1) and IL-33 release, and downstream type-2 inflammation. Secondary infection induced an eosinophilic asthma-like pathophysiology in IPS-1−/− but not WT mice. Mechanistically, we identified that IPS-1 is necessary for pDC recruitment, IFN-α production and viral control. Our findings suggest that TLR7 and RLR signalling work collaboratively to optimally control the host response to pneumovirus infection thereby protecting against viral bronchiolitis and subsequent asthma.Jennifer SimpsonJason P. LynchZhixuan LohVivian ZhangRhiannon B. WerderKirsten SpannSimon PhippsNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-15 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jennifer Simpson Jason P. Lynch Zhixuan Loh Vivian Zhang Rhiannon B. Werder Kirsten Spann Simon Phipps The Absence of Interferon-β Promotor Stimulator-1 (IPS-1) Predisposes to Bronchiolitis and Asthma-like Pathology in Response to Pneumoviral Infection in Mice
description	Abstract Respiratory syncytial virus (RSV)-bronchiolitis is a major cause of infant morbidity and mortality and a risk factor for subsequent asthma. We showed previously that toll-like receptor (TLR)7 in plasmacytoid dendritic cells (pDCs) is critical for protection against bronchiolitis and asthma in mice infected with pneumonia virus of mice (PVM), the mouse homolog of RSV. This lack of redundancy was unexpected as interferon-β promotor stimulator-1 (IPS-1) signalling, downstream of RIG-I-like receptor (RLR) and not TLR7 activation, contributes to host defence in hRSV-inoculated adult mice. To further clarify the role of IPS-1 signalling, we inoculated IPS-1−/− and WT mice with PVM in early-life, and again in later-life, to model the association between bronchiolitis and asthma. IPS-1 deficiency predisposed to severe PVM bronchiolitis, characterised by neutrophilic inflammation and necroptotic airway epithelial cell death, high mobility group box 1 (HMGB1) and IL-33 release, and downstream type-2 inflammation. Secondary infection induced an eosinophilic asthma-like pathophysiology in IPS-1−/− but not WT mice. Mechanistically, we identified that IPS-1 is necessary for pDC recruitment, IFN-α production and viral control. Our findings suggest that TLR7 and RLR signalling work collaboratively to optimally control the host response to pneumovirus infection thereby protecting against viral bronchiolitis and subsequent asthma.
format	article
author	Jennifer Simpson Jason P. Lynch Zhixuan Loh Vivian Zhang Rhiannon B. Werder Kirsten Spann Simon Phipps
author_facet	Jennifer Simpson Jason P. Lynch Zhixuan Loh Vivian Zhang Rhiannon B. Werder Kirsten Spann Simon Phipps
author_sort	Jennifer Simpson
title	The Absence of Interferon-β Promotor Stimulator-1 (IPS-1) Predisposes to Bronchiolitis and Asthma-like Pathology in Response to Pneumoviral Infection in Mice
title_short	The Absence of Interferon-β Promotor Stimulator-1 (IPS-1) Predisposes to Bronchiolitis and Asthma-like Pathology in Response to Pneumoviral Infection in Mice
title_full	The Absence of Interferon-β Promotor Stimulator-1 (IPS-1) Predisposes to Bronchiolitis and Asthma-like Pathology in Response to Pneumoviral Infection in Mice
title_fullStr	The Absence of Interferon-β Promotor Stimulator-1 (IPS-1) Predisposes to Bronchiolitis and Asthma-like Pathology in Response to Pneumoviral Infection in Mice
title_full_unstemmed	The Absence of Interferon-β Promotor Stimulator-1 (IPS-1) Predisposes to Bronchiolitis and Asthma-like Pathology in Response to Pneumoviral Infection in Mice
title_sort	absence of interferon-β promotor stimulator-1 (ips-1) predisposes to bronchiolitis and asthma-like pathology in response to pneumoviral infection in mice
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/16320a97d87d463db6bea7ee5c251f82
work_keys_str_mv	AT jennifersimpson theabsenceofinterferonbpromotorstimulator1ips1predisposestobronchiolitisandasthmalikepathologyinresponsetopneumoviralinfectioninmice AT jasonplynch theabsenceofinterferonbpromotorstimulator1ips1predisposestobronchiolitisandasthmalikepathologyinresponsetopneumoviralinfectioninmice AT zhixuanloh theabsenceofinterferonbpromotorstimulator1ips1predisposestobronchiolitisandasthmalikepathologyinresponsetopneumoviralinfectioninmice AT vivianzhang theabsenceofinterferonbpromotorstimulator1ips1predisposestobronchiolitisandasthmalikepathologyinresponsetopneumoviralinfectioninmice AT rhiannonbwerder theabsenceofinterferonbpromotorstimulator1ips1predisposestobronchiolitisandasthmalikepathologyinresponsetopneumoviralinfectioninmice AT kirstenspann theabsenceofinterferonbpromotorstimulator1ips1predisposestobronchiolitisandasthmalikepathologyinresponsetopneumoviralinfectioninmice AT simonphipps theabsenceofinterferonbpromotorstimulator1ips1predisposestobronchiolitisandasthmalikepathologyinresponsetopneumoviralinfectioninmice AT jennifersimpson absenceofinterferonbpromotorstimulator1ips1predisposestobronchiolitisandasthmalikepathologyinresponsetopneumoviralinfectioninmice AT jasonplynch absenceofinterferonbpromotorstimulator1ips1predisposestobronchiolitisandasthmalikepathologyinresponsetopneumoviralinfectioninmice AT zhixuanloh absenceofinterferonbpromotorstimulator1ips1predisposestobronchiolitisandasthmalikepathologyinresponsetopneumoviralinfectioninmice AT vivianzhang absenceofinterferonbpromotorstimulator1ips1predisposestobronchiolitisandasthmalikepathologyinresponsetopneumoviralinfectioninmice AT rhiannonbwerder absenceofinterferonbpromotorstimulator1ips1predisposestobronchiolitisandasthmalikepathologyinresponsetopneumoviralinfectioninmice AT kirstenspann absenceofinterferonbpromotorstimulator1ips1predisposestobronchiolitisandasthmalikepathologyinresponsetopneumoviralinfectioninmice AT simonphipps absenceofinterferonbpromotorstimulator1ips1predisposestobronchiolitisandasthmalikepathologyinresponsetopneumoviralinfectioninmice
_version_	1718393963440766976

The Absence of Interferon-β Promotor Stimulator-1 (IPS-1) Predisposes to Bronchiolitis and Asthma-like Pathology in Response to Pneumoviral Infection in Mice

Ejemplares similares