Lambda Interferon Restructures the Nasal Microbiome and Increases Susceptibility to <named-content content-type="genus-species">Staphylococcus aureus</named-content> Superinfection

ABSTRACT Much of the morbidity and mortality associated with influenza virus respiratory infection is due to bacterial coinfection with pathogens that colonize the upper respiratory tract such as methicillin-resistant Staphylococcus aureus (MRSA) and Streptococcus pneumoniae. A major component of th...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Paul J. Planet, Dane Parker, Taylor S. Cohen, Hannah Smith, Justinne D. Leon, Chanelle Ryan, Tobin J. Hammer, Noah Fierer, Emily I. Chen, Alice S. Prince
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2016
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/49787d6a198d4200bd7c5c8ac7398470
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:49787d6a198d4200bd7c5c8ac7398470
record_format	dspace
spelling	oai:doaj.org-article:49787d6a198d4200bd7c5c8ac73984702021-11-15T15:49:40ZLambda Interferon Restructures the Nasal Microbiome and Increases Susceptibility to <named-content content-type="genus-species">Staphylococcus aureus</named-content> Superinfection10.1128/mBio.01939-152150-7511https://doaj.org/article/49787d6a198d4200bd7c5c8ac73984702016-03-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01939-15https://doaj.org/toc/2150-7511ABSTRACT Much of the morbidity and mortality associated with influenza virus respiratory infection is due to bacterial coinfection with pathogens that colonize the upper respiratory tract such as methicillin-resistant Staphylococcus aureus (MRSA) and Streptococcus pneumoniae. A major component of the immune response to influenza virus is the production of type I and III interferons. Here we show that the immune response to infection with influenza virus causes an increase and restructuring of the upper respiratory microbiota in wild-type (WT) mice but not in Il28r−/− mutant mice lacking the receptor for type III interferon. Mice lacking the IL-28 receptor fail to induce STAT1 phosphorylation and expression of its regulator, SOCS1. Il28r−/− mutant mice have increased expression of interleukin-22 (IL-22), as well as Ngal and RegIIIγ, in the nasal cavity, the source of organisms that would be aspirated to cause pneumonia. Proteomic analysis reveals changes in several cytoskeletal proteins that contribute to barrier function in the nasal epithelium that may contribute to the effects of IL-28 signaling on the microbiota. The importance of the effects of IL-28 signaling in the pathogenesis of MRSA pneumonia after influenza virus infection was confirmed by showing that WT mice nasally colonized before or after influenza virus infection had significantly higher levels of infection in the upper airways, as well as significantly greater susceptibility to MRSA pneumonia than Il28r−/− mutant mice did. Our results suggest that activation of the type III interferon in response to influenza virus infection has a major effect in expanding the upper airway microbiome and increasing susceptibility to lower respiratory tract infection. IMPORTANCE S. aureus and influenza virus are important respiratory pathogens, and coinfection with these organisms is associated with significant morbidity and mortality. The ability of influenza virus to increase susceptibility to S. aureus infection is less well understood. We show here that influenza virus leads to a change in the upper airway microbiome in a type III interferon-dependent manner. Mice lacking the type III interferon receptor have altered STAT1 and IL-22 signaling. In coinfection studies, mice without the type III interferon receptor had significantly less nasal S. aureus colonization and subsequent pneumonia than infected WT mice did. This work demonstrates that type III interferons induced by influenza virus contribute to nasal colonization and pneumonia due to S. aureus superinfection.Paul J. PlanetDane ParkerTaylor S. CohenHannah SmithJustinne D. LeonChanelle RyanTobin J. HammerNoah FiererEmily I. ChenAlice S. PrinceAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 7, Iss 1 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Paul J. Planet Dane Parker Taylor S. Cohen Hannah Smith Justinne D. Leon Chanelle Ryan Tobin J. Hammer Noah Fierer Emily I. Chen Alice S. Prince Lambda Interferon Restructures the Nasal Microbiome and Increases Susceptibility to <named-content content-type="genus-species">Staphylococcus aureus</named-content> Superinfection
description	ABSTRACT Much of the morbidity and mortality associated with influenza virus respiratory infection is due to bacterial coinfection with pathogens that colonize the upper respiratory tract such as methicillin-resistant Staphylococcus aureus (MRSA) and Streptococcus pneumoniae. A major component of the immune response to influenza virus is the production of type I and III interferons. Here we show that the immune response to infection with influenza virus causes an increase and restructuring of the upper respiratory microbiota in wild-type (WT) mice but not in Il28r−/− mutant mice lacking the receptor for type III interferon. Mice lacking the IL-28 receptor fail to induce STAT1 phosphorylation and expression of its regulator, SOCS1. Il28r−/− mutant mice have increased expression of interleukin-22 (IL-22), as well as Ngal and RegIIIγ, in the nasal cavity, the source of organisms that would be aspirated to cause pneumonia. Proteomic analysis reveals changes in several cytoskeletal proteins that contribute to barrier function in the nasal epithelium that may contribute to the effects of IL-28 signaling on the microbiota. The importance of the effects of IL-28 signaling in the pathogenesis of MRSA pneumonia after influenza virus infection was confirmed by showing that WT mice nasally colonized before or after influenza virus infection had significantly higher levels of infection in the upper airways, as well as significantly greater susceptibility to MRSA pneumonia than Il28r−/− mutant mice did. Our results suggest that activation of the type III interferon in response to influenza virus infection has a major effect in expanding the upper airway microbiome and increasing susceptibility to lower respiratory tract infection. IMPORTANCE S. aureus and influenza virus are important respiratory pathogens, and coinfection with these organisms is associated with significant morbidity and mortality. The ability of influenza virus to increase susceptibility to S. aureus infection is less well understood. We show here that influenza virus leads to a change in the upper airway microbiome in a type III interferon-dependent manner. Mice lacking the type III interferon receptor have altered STAT1 and IL-22 signaling. In coinfection studies, mice without the type III interferon receptor had significantly less nasal S. aureus colonization and subsequent pneumonia than infected WT mice did. This work demonstrates that type III interferons induced by influenza virus contribute to nasal colonization and pneumonia due to S. aureus superinfection.
format	article
author	Paul J. Planet Dane Parker Taylor S. Cohen Hannah Smith Justinne D. Leon Chanelle Ryan Tobin J. Hammer Noah Fierer Emily I. Chen Alice S. Prince
author_facet	Paul J. Planet Dane Parker Taylor S. Cohen Hannah Smith Justinne D. Leon Chanelle Ryan Tobin J. Hammer Noah Fierer Emily I. Chen Alice S. Prince
author_sort	Paul J. Planet
title	Lambda Interferon Restructures the Nasal Microbiome and Increases Susceptibility to <named-content content-type="genus-species">Staphylococcus aureus</named-content> Superinfection
title_short	Lambda Interferon Restructures the Nasal Microbiome and Increases Susceptibility to <named-content content-type="genus-species">Staphylococcus aureus</named-content> Superinfection
title_full	Lambda Interferon Restructures the Nasal Microbiome and Increases Susceptibility to <named-content content-type="genus-species">Staphylococcus aureus</named-content> Superinfection
title_fullStr	Lambda Interferon Restructures the Nasal Microbiome and Increases Susceptibility to <named-content content-type="genus-species">Staphylococcus aureus</named-content> Superinfection
title_full_unstemmed	Lambda Interferon Restructures the Nasal Microbiome and Increases Susceptibility to <named-content content-type="genus-species">Staphylococcus aureus</named-content> Superinfection
title_sort	lambda interferon restructures the nasal microbiome and increases susceptibility to <named-content content-type="genus-species">staphylococcus aureus</named-content> superinfection
publisher	American Society for Microbiology
publishDate	2016
url	https://doaj.org/article/49787d6a198d4200bd7c5c8ac7398470
work_keys_str_mv	AT pauljplanet lambdainterferonrestructuresthenasalmicrobiomeandincreasessusceptibilitytonamedcontentcontenttypegenusspeciesstaphylococcusaureusnamedcontentsuperinfection AT daneparker lambdainterferonrestructuresthenasalmicrobiomeandincreasessusceptibilitytonamedcontentcontenttypegenusspeciesstaphylococcusaureusnamedcontentsuperinfection AT taylorscohen lambdainterferonrestructuresthenasalmicrobiomeandincreasessusceptibilitytonamedcontentcontenttypegenusspeciesstaphylococcusaureusnamedcontentsuperinfection AT hannahsmith lambdainterferonrestructuresthenasalmicrobiomeandincreasessusceptibilitytonamedcontentcontenttypegenusspeciesstaphylococcusaureusnamedcontentsuperinfection AT justinnedleon lambdainterferonrestructuresthenasalmicrobiomeandincreasessusceptibilitytonamedcontentcontenttypegenusspeciesstaphylococcusaureusnamedcontentsuperinfection AT chanelleryan lambdainterferonrestructuresthenasalmicrobiomeandincreasessusceptibilitytonamedcontentcontenttypegenusspeciesstaphylococcusaureusnamedcontentsuperinfection AT tobinjhammer lambdainterferonrestructuresthenasalmicrobiomeandincreasessusceptibilitytonamedcontentcontenttypegenusspeciesstaphylococcusaureusnamedcontentsuperinfection AT noahfierer lambdainterferonrestructuresthenasalmicrobiomeandincreasessusceptibilitytonamedcontentcontenttypegenusspeciesstaphylococcusaureusnamedcontentsuperinfection AT emilyichen lambdainterferonrestructuresthenasalmicrobiomeandincreasessusceptibilitytonamedcontentcontenttypegenusspeciesstaphylococcusaureusnamedcontentsuperinfection AT alicesprince lambdainterferonrestructuresthenasalmicrobiomeandincreasessusceptibilitytonamedcontentcontenttypegenusspeciesstaphylococcusaureusnamedcontentsuperinfection
_version_	1718427455183650816

Lambda Interferon Restructures the Nasal Microbiome and Increases Susceptibility to <named-content content-type="genus-species">Staphylococcus aureus</named-content> Superinfection

Ejemplares similares