Intranasal Bifidobacterium longum protects against viral-induced lung inflammation and injury in a murine model of lethal influenza infection

Background: Prophylactic strategies are urgently needed for prevention of severe inflammatory responses to respiratory viral infections. Bacterial-host interactions may modify the immune response to viral infections. Methods: We examined the contribution of Intranasal administration of two different...

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Main Authors: David Groeger, Elisa Schiavi, Ray Grant, Magdalena Kurnik-Łucka, David Michalovich, Rick Williamson, Soren Beinke, Barry Kiely, Cezmi A Akdis, Edith M Hessel, Fergus Shanahan, Liam O’ Mahony
Format: Article
Language:English
Published: Elsevier 2020-10-01
Series:EBioMedicine
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Online Access:http://www.sciencedirect.com/science/article/pii/S2352396420303571
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author David Groeger
Elisa Schiavi
Ray Grant
Magdalena Kurnik-Łucka
David Michalovich
Rick Williamson
Soren Beinke
Barry Kiely
Cezmi A Akdis
Edith M Hessel
Fergus Shanahan
Liam O’ Mahony
author_facet David Groeger
Elisa Schiavi
Ray Grant
Magdalena Kurnik-Łucka
David Michalovich
Rick Williamson
Soren Beinke
Barry Kiely
Cezmi A Akdis
Edith M Hessel
Fergus Shanahan
Liam O’ Mahony
author_sort David Groeger
collection DOAJ
description Background: Prophylactic strategies are urgently needed for prevention of severe inflammatory responses to respiratory viral infections. Bacterial-host interactions may modify the immune response to viral infections. Methods: We examined the contribution of Intranasal administration of two different Bifidobacterium longum strains or its isolated cell wall in controlling viral induced inflammation using a murine model of influenza infection. We monitored mortality and morbidity over a 10-day period and viral load, differential broncho alveolar lavage (BAL) fluid inflammatory cell counts, Lung tissue histology, BAL and serum cytokines, markers of vascular damage and cell death were quantified. Findings: Intranasal administration of Bifidobacterium longum 35624® or its isolated cell wall prior to virus inoculation significantly reduced viral load within the lungs and significantly improved survival. Reduced viral load was associated with reduced lung injury as suggested by cell death and vascular leakage markers, a shift from neutrophil to macrophage recruitment, reduced inflammatory cytokine levels (including IL-6), reduced type 1 and 2 interferon levels, but increased levels of interferon-λ and surfactant protein D. These protective effects were maintained when the bifidobacterial cell wall preparation was administered 24 h after viral inoculation. The protective effects were also observed for the Bifidobacterium longum PB-VIR™ strain. Interpretation: Exposure to these bifidobacterial strains protect against the inflammatory sequelae and damage associated with uncontrolled viral replication within the lung. Funding: This work has been funded, in part, by a research grant from GlaxoSmithKline, PrecisionBiotics Group Ltd., Swiss National Science Foundation grants (project numbers CRSII3_154488, 310030_144219, 310030_127356 and 310030_144219) and Christine Kühne – Center for Allergy Research and Education (CK-CARE).
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spelling doaj.art-c79e7c7b3ea44122b4eb1b59c03327962022-12-22T01:30:48ZengElsevierEBioMedicine2352-39642020-10-0160102981Intranasal Bifidobacterium longum protects against viral-induced lung inflammation and injury in a murine model of lethal influenza infectionDavid Groeger0Elisa Schiavi1Ray Grant2Magdalena Kurnik-Łucka3David Michalovich4Rick Williamson5Soren Beinke6Barry Kiely7Cezmi A Akdis8Edith M Hessel9Fergus Shanahan10Liam O’ Mahony11Alimentary Health Pharma Davos, Davos, Switzerland; PrecisionBiotics Group Ltd., Cork, Ireland; Lead contact; Corresponding author.Alimentary Health Pharma Davos, Davos, Switzerland; Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, SwitzerlandAlimentary Health Pharma Davos, Davos, SwitzerlandDepartment of Pathophysiology, Jagiellonian University Medical College, Krakow, PolandGSK, Stevenage, United KingdomGSK, Stevenage, United KingdomGSK, Stevenage, United KingdomPrecisionBiotics Group Ltd., Cork, IrelandSwiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, SwitzerlandGSK, Stevenage, United KingdomDepartment of Medicine and School of Microbiology, APC Microbiome Ireland, National University of Ireland, Cork, IrelandDepartment of Medicine and School of Microbiology, APC Microbiome Ireland, National University of Ireland, Cork, IrelandBackground: Prophylactic strategies are urgently needed for prevention of severe inflammatory responses to respiratory viral infections. Bacterial-host interactions may modify the immune response to viral infections. Methods: We examined the contribution of Intranasal administration of two different Bifidobacterium longum strains or its isolated cell wall in controlling viral induced inflammation using a murine model of influenza infection. We monitored mortality and morbidity over a 10-day period and viral load, differential broncho alveolar lavage (BAL) fluid inflammatory cell counts, Lung tissue histology, BAL and serum cytokines, markers of vascular damage and cell death were quantified. Findings: Intranasal administration of Bifidobacterium longum 35624® or its isolated cell wall prior to virus inoculation significantly reduced viral load within the lungs and significantly improved survival. Reduced viral load was associated with reduced lung injury as suggested by cell death and vascular leakage markers, a shift from neutrophil to macrophage recruitment, reduced inflammatory cytokine levels (including IL-6), reduced type 1 and 2 interferon levels, but increased levels of interferon-λ and surfactant protein D. These protective effects were maintained when the bifidobacterial cell wall preparation was administered 24 h after viral inoculation. The protective effects were also observed for the Bifidobacterium longum PB-VIR™ strain. Interpretation: Exposure to these bifidobacterial strains protect against the inflammatory sequelae and damage associated with uncontrolled viral replication within the lung. Funding: This work has been funded, in part, by a research grant from GlaxoSmithKline, PrecisionBiotics Group Ltd., Swiss National Science Foundation grants (project numbers CRSII3_154488, 310030_144219, 310030_127356 and 310030_144219) and Christine Kühne – Center for Allergy Research and Education (CK-CARE).http://www.sciencedirect.com/science/article/pii/S2352396420303571InfluenzaProbioticInterferonPrevention
spellingShingle David Groeger
Elisa Schiavi
Ray Grant
Magdalena Kurnik-Łucka
David Michalovich
Rick Williamson
Soren Beinke
Barry Kiely
Cezmi A Akdis
Edith M Hessel
Fergus Shanahan
Liam O’ Mahony
Intranasal Bifidobacterium longum protects against viral-induced lung inflammation and injury in a murine model of lethal influenza infection
EBioMedicine
Influenza
Probiotic
Interferon
Prevention
title Intranasal Bifidobacterium longum protects against viral-induced lung inflammation and injury in a murine model of lethal influenza infection
title_full Intranasal Bifidobacterium longum protects against viral-induced lung inflammation and injury in a murine model of lethal influenza infection
title_fullStr Intranasal Bifidobacterium longum protects against viral-induced lung inflammation and injury in a murine model of lethal influenza infection
title_full_unstemmed Intranasal Bifidobacterium longum protects against viral-induced lung inflammation and injury in a murine model of lethal influenza infection
title_short Intranasal Bifidobacterium longum protects against viral-induced lung inflammation and injury in a murine model of lethal influenza infection
title_sort intranasal bifidobacterium longum protects against viral induced lung inflammation and injury in a murine model of lethal influenza infection
topic Influenza
Probiotic
Interferon
Prevention
url http://www.sciencedirect.com/science/article/pii/S2352396420303571
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