Exogenous Activation of Invariant Natural Killer T Cells by α-Galactosylceramide Reduces Pneumococcal Outgrowth and Dissemination Postinfluenza

ABSTRACT Influenza A virus infection can predispose to potentially devastating secondary bacterial infections. Invariant natural killer T (iNKT) cells are unconventional, lipid-reactive T lymphocytes that exert potent immunostimulatory functions. Using a mouse model of postinfluenza invasive seconda...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Adeline Barthelemy, Stoyan Ivanov, Maya Hassane, Josette Fontaine, Béatrice Heurtault, Benoit Frisch, Christelle Faveeuw, Christophe Paget, François Trottein
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2016
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/ea9a7c2a76684b4fa5d88da07712982a
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:ea9a7c2a76684b4fa5d88da07712982a
record_format	dspace
spelling	oai:doaj.org-article:ea9a7c2a76684b4fa5d88da07712982a2021-11-15T15:50:15ZExogenous Activation of Invariant Natural Killer T Cells by α-Galactosylceramide Reduces Pneumococcal Outgrowth and Dissemination Postinfluenza10.1128/mBio.01440-162150-7511https://doaj.org/article/ea9a7c2a76684b4fa5d88da07712982a2016-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01440-16https://doaj.org/toc/2150-7511ABSTRACT Influenza A virus infection can predispose to potentially devastating secondary bacterial infections. Invariant natural killer T (iNKT) cells are unconventional, lipid-reactive T lymphocytes that exert potent immunostimulatory functions. Using a mouse model of postinfluenza invasive secondary pneumococcal infection, we sought to establish whether α-galactosylceramide (α-GalCer [a potent iNKT cell agonist that is currently in clinical development]) could limit bacterial superinfection. Our results highlighted the presence of a critical time window during which α-GalCer treatment can trigger iNKT cell activation and influence resistance to postinfluenza secondary pneumococcal infection. Intranasal treatment with α-GalCer during the acute phase (on day 7) of influenza virus H3N2 and H1N1 infection failed to activate (gamma interferon [IFN-γ] and interleukin-17A [IL-17A]) iNKT cells; this effect was associated with a strongly reduced number of conventional CD103+ dendritic cells in the respiratory tract. In contrast, α-GalCer treatment during the early phase (on day 4) or during the resolution phase (day 14) of influenza was associated with lower pneumococcal outgrowth and dissemination. Less intense viral-bacterial pneumonia and a lower morbidity rate were observed in superinfected mice treated with both α-GalCer (day 14) and the corticosteroid dexamethasone. Our results open the way to alternative (nonantiviral/nonantibiotic) iNKT-cell-based approaches for limiting postinfluenza secondary bacterial infections. IMPORTANCE Despite the application of vaccination programs and antiviral drugs, influenza A virus (IAV) infection is responsible for widespread morbidity and mortality (500,000 deaths/year). Influenza infections can also result in sporadic pandemics that can be devastating: the 1918 pandemic led to the death of 50 million people. Severe bacterial infections are commonly associated with influenza and are significant contributors to the excess morbidity and mortality of influenza. Today’s treatments of secondary bacterial (pneumococcal) infections are still not effective enough, and antibiotic resistance is a major issue. Hence, there is an urgent need for novel therapies. In the present study, we set out to evaluate the efficacy of α-galactosylceramide (α-GalCer)—a potent agonist of invariant NKT cells that is currently in clinical development—in a mouse model of postinfluenza, highly invasive pneumococcal pneumonia. Our data indicate that treatment with α-GalCer reduces susceptibility to superinfections and, when combined with the corticosteroid dexamethasone, reduces viral-bacterial pneumonia.Adeline BarthelemyStoyan IvanovMaya HassaneJosette FontaineBéatrice HeurtaultBenoit FrischChristelle FaveeuwChristophe PagetFrançois TrotteinAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 7, Iss 6 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Adeline Barthelemy Stoyan Ivanov Maya Hassane Josette Fontaine Béatrice Heurtault Benoit Frisch Christelle Faveeuw Christophe Paget François Trottein Exogenous Activation of Invariant Natural Killer T Cells by α-Galactosylceramide Reduces Pneumococcal Outgrowth and Dissemination Postinfluenza
description	ABSTRACT Influenza A virus infection can predispose to potentially devastating secondary bacterial infections. Invariant natural killer T (iNKT) cells are unconventional, lipid-reactive T lymphocytes that exert potent immunostimulatory functions. Using a mouse model of postinfluenza invasive secondary pneumococcal infection, we sought to establish whether α-galactosylceramide (α-GalCer [a potent iNKT cell agonist that is currently in clinical development]) could limit bacterial superinfection. Our results highlighted the presence of a critical time window during which α-GalCer treatment can trigger iNKT cell activation and influence resistance to postinfluenza secondary pneumococcal infection. Intranasal treatment with α-GalCer during the acute phase (on day 7) of influenza virus H3N2 and H1N1 infection failed to activate (gamma interferon [IFN-γ] and interleukin-17A [IL-17A]) iNKT cells; this effect was associated with a strongly reduced number of conventional CD103+ dendritic cells in the respiratory tract. In contrast, α-GalCer treatment during the early phase (on day 4) or during the resolution phase (day 14) of influenza was associated with lower pneumococcal outgrowth and dissemination. Less intense viral-bacterial pneumonia and a lower morbidity rate were observed in superinfected mice treated with both α-GalCer (day 14) and the corticosteroid dexamethasone. Our results open the way to alternative (nonantiviral/nonantibiotic) iNKT-cell-based approaches for limiting postinfluenza secondary bacterial infections. IMPORTANCE Despite the application of vaccination programs and antiviral drugs, influenza A virus (IAV) infection is responsible for widespread morbidity and mortality (500,000 deaths/year). Influenza infections can also result in sporadic pandemics that can be devastating: the 1918 pandemic led to the death of 50 million people. Severe bacterial infections are commonly associated with influenza and are significant contributors to the excess morbidity and mortality of influenza. Today’s treatments of secondary bacterial (pneumococcal) infections are still not effective enough, and antibiotic resistance is a major issue. Hence, there is an urgent need for novel therapies. In the present study, we set out to evaluate the efficacy of α-galactosylceramide (α-GalCer)—a potent agonist of invariant NKT cells that is currently in clinical development—in a mouse model of postinfluenza, highly invasive pneumococcal pneumonia. Our data indicate that treatment with α-GalCer reduces susceptibility to superinfections and, when combined with the corticosteroid dexamethasone, reduces viral-bacterial pneumonia.
format	article
author	Adeline Barthelemy Stoyan Ivanov Maya Hassane Josette Fontaine Béatrice Heurtault Benoit Frisch Christelle Faveeuw Christophe Paget François Trottein
author_facet	Adeline Barthelemy Stoyan Ivanov Maya Hassane Josette Fontaine Béatrice Heurtault Benoit Frisch Christelle Faveeuw Christophe Paget François Trottein
author_sort	Adeline Barthelemy
title	Exogenous Activation of Invariant Natural Killer T Cells by α-Galactosylceramide Reduces Pneumococcal Outgrowth and Dissemination Postinfluenza
title_short	Exogenous Activation of Invariant Natural Killer T Cells by α-Galactosylceramide Reduces Pneumococcal Outgrowth and Dissemination Postinfluenza
title_full	Exogenous Activation of Invariant Natural Killer T Cells by α-Galactosylceramide Reduces Pneumococcal Outgrowth and Dissemination Postinfluenza
title_fullStr	Exogenous Activation of Invariant Natural Killer T Cells by α-Galactosylceramide Reduces Pneumococcal Outgrowth and Dissemination Postinfluenza
title_full_unstemmed	Exogenous Activation of Invariant Natural Killer T Cells by α-Galactosylceramide Reduces Pneumococcal Outgrowth and Dissemination Postinfluenza
title_sort	exogenous activation of invariant natural killer t cells by α-galactosylceramide reduces pneumococcal outgrowth and dissemination postinfluenza
publisher	American Society for Microbiology
publishDate	2016
url	https://doaj.org/article/ea9a7c2a76684b4fa5d88da07712982a
work_keys_str_mv	AT adelinebarthelemy exogenousactivationofinvariantnaturalkillertcellsbyagalactosylceramidereducespneumococcaloutgrowthanddisseminationpostinfluenza AT stoyanivanov exogenousactivationofinvariantnaturalkillertcellsbyagalactosylceramidereducespneumococcaloutgrowthanddisseminationpostinfluenza AT mayahassane exogenousactivationofinvariantnaturalkillertcellsbyagalactosylceramidereducespneumococcaloutgrowthanddisseminationpostinfluenza AT josettefontaine exogenousactivationofinvariantnaturalkillertcellsbyagalactosylceramidereducespneumococcaloutgrowthanddisseminationpostinfluenza AT beatriceheurtault exogenousactivationofinvariantnaturalkillertcellsbyagalactosylceramidereducespneumococcaloutgrowthanddisseminationpostinfluenza AT benoitfrisch exogenousactivationofinvariantnaturalkillertcellsbyagalactosylceramidereducespneumococcaloutgrowthanddisseminationpostinfluenza AT christellefaveeuw exogenousactivationofinvariantnaturalkillertcellsbyagalactosylceramidereducespneumococcaloutgrowthanddisseminationpostinfluenza AT christophepaget exogenousactivationofinvariantnaturalkillertcellsbyagalactosylceramidereducespneumococcaloutgrowthanddisseminationpostinfluenza AT francoistrottein exogenousactivationofinvariantnaturalkillertcellsbyagalactosylceramidereducespneumococcaloutgrowthanddisseminationpostinfluenza
_version_	1718427494829260800

Exogenous Activation of Invariant Natural Killer T Cells by α-Galactosylceramide Reduces Pneumococcal Outgrowth and Dissemination Postinfluenza

Ejemplares similares