<named-content content-type="genus-species">Streptococcus pneumoniae</named-content> DNA Initiates Type I Interferon Signaling in the Respiratory Tract

ABSTRACT The mucosal epithelium is the initial target for respiratory pathogens of all types. While type I interferon (IFN) signaling is traditionally associated with antiviral immunity, we demonstrate that the extracellular bacterial pathogen Streptococcus pneumoniae activates the type I IFN cascad...

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Autores principales:	Dane Parker, Francis J. Martin, Grace Soong, Bryan S. Harfenist, Jorge L. Aguilar, Adam J. Ratner, Katherine A. Fitzgerald, Christian Schindler, Alice Prince
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2011
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/b3a77f0a43e84d22a60fc0756b78c7d0
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spelling	oai:doaj.org-article:b3a77f0a43e84d22a60fc0756b78c7d02021-11-15T15:38:50Z<named-content content-type="genus-species">Streptococcus pneumoniae</named-content> DNA Initiates Type I Interferon Signaling in the Respiratory Tract10.1128/mBio.00016-112150-7511https://doaj.org/article/b3a77f0a43e84d22a60fc0756b78c7d02011-07-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00016-11https://doaj.org/toc/2150-7511ABSTRACT The mucosal epithelium is the initial target for respiratory pathogens of all types. While type I interferon (IFN) signaling is traditionally associated with antiviral immunity, we demonstrate that the extracellular bacterial pathogen Streptococcus pneumoniae activates the type I IFN cascade in airway epithelial and dendritic cells. This response is dependent upon the pore-forming toxin pneumolysin. Pneumococcal DNA activates IFN-β expression through a DAI/STING/TBK1/IRF3 cascade. Tlr4−/−, Myd88−/−, Trif−/−, and Nod2−/− mutant mice had no impairment of type I IFN signaling. Induction of type I IFN signaling contributes to the eradication of pneumococcal carriage, as IFN-α/β receptor null mice had significantly increased nasal colonization with S. pneumoniae compared with that of wild-type mice. These studies suggest that the type I IFN cascade is a central component of the mucosal response to airway bacterial pathogens and is responsive to bacterial pathogen-associated molecular patterns that are capable of accessing intracellular receptors. IMPORTANCE The bacterium Streptococcus pneumoniae is a leading cause of bacterial pneumonia, leading to upwards of one million deaths a year worldwide and significant economic burden. Although it is known that antibody is critical for efficient phagocytosis, it is not known how this pathogen is sensed by the mucosal epithelium. We demonstrate that this extracellular pathogen activates mucosal signaling typically activated by viral pathogens via the pneumolysin pore to activate intracellular receptors and the type I interferon (IFN) cascade. Mice lacking the receptor to type I IFNs have a reduced ability to clear S. pneumoniae, suggesting that the type I IFN cascade is central to the mucosal clearance of this important pathogen.Dane ParkerFrancis J. MartinGrace SoongBryan S. HarfenistJorge L. AguilarAdam J. RatnerKatherine A. FitzgeraldChristian SchindlerAlice PrinceAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 2, Iss 3 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Dane Parker Francis J. Martin Grace Soong Bryan S. Harfenist Jorge L. Aguilar Adam J. Ratner Katherine A. Fitzgerald Christian Schindler Alice Prince <named-content content-type="genus-species">Streptococcus pneumoniae</named-content> DNA Initiates Type I Interferon Signaling in the Respiratory Tract
description	ABSTRACT The mucosal epithelium is the initial target for respiratory pathogens of all types. While type I interferon (IFN) signaling is traditionally associated with antiviral immunity, we demonstrate that the extracellular bacterial pathogen Streptococcus pneumoniae activates the type I IFN cascade in airway epithelial and dendritic cells. This response is dependent upon the pore-forming toxin pneumolysin. Pneumococcal DNA activates IFN-β expression through a DAI/STING/TBK1/IRF3 cascade. Tlr4−/−, Myd88−/−, Trif−/−, and Nod2−/− mutant mice had no impairment of type I IFN signaling. Induction of type I IFN signaling contributes to the eradication of pneumococcal carriage, as IFN-α/β receptor null mice had significantly increased nasal colonization with S. pneumoniae compared with that of wild-type mice. These studies suggest that the type I IFN cascade is a central component of the mucosal response to airway bacterial pathogens and is responsive to bacterial pathogen-associated molecular patterns that are capable of accessing intracellular receptors. IMPORTANCE The bacterium Streptococcus pneumoniae is a leading cause of bacterial pneumonia, leading to upwards of one million deaths a year worldwide and significant economic burden. Although it is known that antibody is critical for efficient phagocytosis, it is not known how this pathogen is sensed by the mucosal epithelium. We demonstrate that this extracellular pathogen activates mucosal signaling typically activated by viral pathogens via the pneumolysin pore to activate intracellular receptors and the type I interferon (IFN) cascade. Mice lacking the receptor to type I IFNs have a reduced ability to clear S. pneumoniae, suggesting that the type I IFN cascade is central to the mucosal clearance of this important pathogen.
format	article
author	Dane Parker Francis J. Martin Grace Soong Bryan S. Harfenist Jorge L. Aguilar Adam J. Ratner Katherine A. Fitzgerald Christian Schindler Alice Prince
author_facet	Dane Parker Francis J. Martin Grace Soong Bryan S. Harfenist Jorge L. Aguilar Adam J. Ratner Katherine A. Fitzgerald Christian Schindler Alice Prince
author_sort	Dane Parker
title	<named-content content-type="genus-species">Streptococcus pneumoniae</named-content> DNA Initiates Type I Interferon Signaling in the Respiratory Tract
title_short	<named-content content-type="genus-species">Streptococcus pneumoniae</named-content> DNA Initiates Type I Interferon Signaling in the Respiratory Tract
title_full	<named-content content-type="genus-species">Streptococcus pneumoniae</named-content> DNA Initiates Type I Interferon Signaling in the Respiratory Tract
title_fullStr	<named-content content-type="genus-species">Streptococcus pneumoniae</named-content> DNA Initiates Type I Interferon Signaling in the Respiratory Tract
title_full_unstemmed	<named-content content-type="genus-species">Streptococcus pneumoniae</named-content> DNA Initiates Type I Interferon Signaling in the Respiratory Tract
title_sort	<named-content content-type="genus-species">streptococcus pneumoniae</named-content> dna initiates type i interferon signaling in the respiratory tract
publisher	American Society for Microbiology
publishDate	2011
url	https://doaj.org/article/b3a77f0a43e84d22a60fc0756b78c7d0
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<named-content content-type="genus-species">Streptococcus pneumoniae</named-content> DNA Initiates Type I Interferon Signaling in the Respiratory Tract

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