Innate Immune Training with Bacterial Extracts Enhances Lung Macrophage Recruitment to Protect from Betacoronavirus Infection

Training of the innate immune system with orally ingested bacterial extracts was demonstrated to have beneficial effects on infection clearance and disease outcome. The aim of our study was to identify cellular and molecular processes responsible for these immunological benefits. We used a murine co...

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Autores principales: Manuel Salzmann, Patrick Haider, Christoph Kaun, Mira Brekalo, Boris Hartmann, Theresia Lengheimer, Rebecca Pichler, Thomas Filip, Sophia Derdak, Bruno Podesser, Christian Hengstenberg, Walter S. Speidl, Johann Wojta, Roberto Plasenzotti, Philipp J. Hohensinner
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Publicado: Karger Publishers 2021
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Acceso en línea:https://doaj.org/article/29d288b1ebad47b4a34ad65a3bd7db21
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spelling oai:doaj.org-article:29d288b1ebad47b4a34ad65a3bd7db212021-12-02T12:40:22ZInnate Immune Training with Bacterial Extracts Enhances Lung Macrophage Recruitment to Protect from Betacoronavirus Infection1662-811X1662-812810.1159/000519699https://doaj.org/article/29d288b1ebad47b4a34ad65a3bd7db212021-11-01T00:00:00Zhttps://www.karger.com/Article/FullText/519699https://doaj.org/toc/1662-811Xhttps://doaj.org/toc/1662-8128Training of the innate immune system with orally ingested bacterial extracts was demonstrated to have beneficial effects on infection clearance and disease outcome. The aim of our study was to identify cellular and molecular processes responsible for these immunological benefits. We used a murine coronavirus (MCoV) A59 mouse model treated with the immune activating bacterial extract Broncho-Vaxom (BV) OM-85. Tissue samples were analysed with qPCR, RNA sequencing, histology, and flow cytometry. After BV OM-85 treatment, interstitial macrophages accumulated in lung tissue leading to a faster response of type I interferon (IFN) signalling after MCoV infection resulting in overall lung tissue protection. Moreover, RNA sequencing showed that lung tissue from mice receiving BV OM-85 resembled an intermediate stage between healthy and viral infected lung tissue at day 4, indicating a faster return to normal tissue homoeostasis. The pharmacologic effect was mimicked by adoptively transferring naive lung macrophages into lungs from recipient mice before virus infection. The beneficial effect of BV OM-85 was abolished when inhibiting initial type I IFN signalling. Overall, our data suggest that BV OM-85 enhances lung macrophages allowing for a faster IFN response towards a viral challenge as part of the oral-induced innate immune system training.Manuel SalzmannPatrick HaiderChristoph KaunMira BrekaloBoris HartmannTheresia LengheimerRebecca PichlerThomas FilipSophia DerdakBruno PodesserChristian HengstenbergWalter S. SpeidlJohann WojtaRoberto PlasenzottiPhilipp J. HohensinnerKarger Publishersarticlemacrophagetrained immunitybacterial extractmouse coronavirusMedicineRInternal medicineRC31-1245ENJournal of Innate Immunity, Pp 1-13 (2021)
institution DOAJ
collection DOAJ
language EN
topic macrophage
trained immunity
bacterial extract
mouse coronavirus
Medicine
R
Internal medicine
RC31-1245
spellingShingle macrophage
trained immunity
bacterial extract
mouse coronavirus
Medicine
R
Internal medicine
RC31-1245
Manuel Salzmann
Patrick Haider
Christoph Kaun
Mira Brekalo
Boris Hartmann
Theresia Lengheimer
Rebecca Pichler
Thomas Filip
Sophia Derdak
Bruno Podesser
Christian Hengstenberg
Walter S. Speidl
Johann Wojta
Roberto Plasenzotti
Philipp J. Hohensinner
Innate Immune Training with Bacterial Extracts Enhances Lung Macrophage Recruitment to Protect from Betacoronavirus Infection
description Training of the innate immune system with orally ingested bacterial extracts was demonstrated to have beneficial effects on infection clearance and disease outcome. The aim of our study was to identify cellular and molecular processes responsible for these immunological benefits. We used a murine coronavirus (MCoV) A59 mouse model treated with the immune activating bacterial extract Broncho-Vaxom (BV) OM-85. Tissue samples were analysed with qPCR, RNA sequencing, histology, and flow cytometry. After BV OM-85 treatment, interstitial macrophages accumulated in lung tissue leading to a faster response of type I interferon (IFN) signalling after MCoV infection resulting in overall lung tissue protection. Moreover, RNA sequencing showed that lung tissue from mice receiving BV OM-85 resembled an intermediate stage between healthy and viral infected lung tissue at day 4, indicating a faster return to normal tissue homoeostasis. The pharmacologic effect was mimicked by adoptively transferring naive lung macrophages into lungs from recipient mice before virus infection. The beneficial effect of BV OM-85 was abolished when inhibiting initial type I IFN signalling. Overall, our data suggest that BV OM-85 enhances lung macrophages allowing for a faster IFN response towards a viral challenge as part of the oral-induced innate immune system training.
format article
author Manuel Salzmann
Patrick Haider
Christoph Kaun
Mira Brekalo
Boris Hartmann
Theresia Lengheimer
Rebecca Pichler
Thomas Filip
Sophia Derdak
Bruno Podesser
Christian Hengstenberg
Walter S. Speidl
Johann Wojta
Roberto Plasenzotti
Philipp J. Hohensinner
author_facet Manuel Salzmann
Patrick Haider
Christoph Kaun
Mira Brekalo
Boris Hartmann
Theresia Lengheimer
Rebecca Pichler
Thomas Filip
Sophia Derdak
Bruno Podesser
Christian Hengstenberg
Walter S. Speidl
Johann Wojta
Roberto Plasenzotti
Philipp J. Hohensinner
author_sort Manuel Salzmann
title Innate Immune Training with Bacterial Extracts Enhances Lung Macrophage Recruitment to Protect from Betacoronavirus Infection
title_short Innate Immune Training with Bacterial Extracts Enhances Lung Macrophage Recruitment to Protect from Betacoronavirus Infection
title_full Innate Immune Training with Bacterial Extracts Enhances Lung Macrophage Recruitment to Protect from Betacoronavirus Infection
title_fullStr Innate Immune Training with Bacterial Extracts Enhances Lung Macrophage Recruitment to Protect from Betacoronavirus Infection
title_full_unstemmed Innate Immune Training with Bacterial Extracts Enhances Lung Macrophage Recruitment to Protect from Betacoronavirus Infection
title_sort innate immune training with bacterial extracts enhances lung macrophage recruitment to protect from betacoronavirus infection
publisher Karger Publishers
publishDate 2021
url https://doaj.org/article/29d288b1ebad47b4a34ad65a3bd7db21
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