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  1. Article ; Online: The OM-85 bacterial lysate inhibits SARS-CoV-2 infection of epithelial cells by downregulating SARS-CoV-2 receptor expression.

    Pivniouk, Vadim / Pivniouk, Oksana / DeVries, Avery / Uhrlaub, Jennifer L / Michael, Ashley / Pivniouk, Denis / VanLinden, Sydney R / Conway, Michelle Y / Hahn, Seongmin / Malone, Sean P / Ezeh, Peace / Churko, Jared M / Anderson, Dayna / Kraft, Monica / Nikolich-Zugich, Janko / Vercelli, Donata

    The Journal of allergy and clinical immunology

    2021  Volume 149, Issue 3, Page(s) 923–933.e6

    Abstract: Background: Treatments for coronavirus disease 2019, which is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), are urgently needed but remain limited. SARS-CoV-2 infects cells through interactions of its spike (S) protein with ... ...

    Abstract Background: Treatments for coronavirus disease 2019, which is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), are urgently needed but remain limited. SARS-CoV-2 infects cells through interactions of its spike (S) protein with angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) on host cells. Multiple cells and organs are targeted, particularly airway epithelial cells. OM-85, a standardized lysate of human airway bacteria with strong immunomodulating properties and an impeccable safety profile, is widely used to prevent recurrent respiratory infections. We found that airway OM-85 administration inhibits Ace2 and Tmprss2 transcription in the mouse lung, suggesting that OM-85 might hinder SARS-CoV-2/host cell interactions.
    Objectives: We sought to investigate whether and how OM-85 treatment protects nonhuman primate and human epithelial cells against SARS-CoV-2.
    Methods: ACE2 and TMPRSS2 mRNA and protein expression, cell binding of SARS-CoV-2 S1 protein, cell entry of SARS-CoV-2 S protein-pseudotyped lentiviral particles, and SARS-CoV-2 cell infection were measured in kidney, lung, and intestinal epithelial cell lines, primary human bronchial epithelial cells, and ACE2-transfected HEK293T cells treated with OM-85 in vitro.
    Results: OM-85 significantly downregulated ACE2 and TMPRSS2 transcription and surface ACE2 protein expression in epithelial cell lines and primary bronchial epithelial cells. OM-85 also strongly inhibited SARS-CoV-2 S1 protein binding to, SARS-CoV-2 S protein-pseudotyped lentivirus entry into, and SARS-CoV-2 infection of epithelial cells. These effects of OM-85 appeared to depend on SARS-CoV-2 receptor downregulation.
    Conclusions: OM-85 inhibits SARS-CoV-2 epithelial cell infection in vitro by downregulating SARS-CoV-2 receptor expression. Further studies are warranted to assess whether OM-85 may prevent and/or reduce the severity of coronavirus disease 2019.
    MeSH term(s) Adjuvants, Immunologic/administration & dosage ; Angiotensin-Converting Enzyme 2/antagonists & inhibitors ; Angiotensin-Converting Enzyme 2/genetics ; Angiotensin-Converting Enzyme 2/immunology ; Animals ; COVID-19/immunology ; COVID-19/prevention & control ; COVID-19/virology ; Caco-2 Cells ; Cell Extracts/administration & dosage ; Cell Extracts/immunology ; Cells, Cultured ; Chlorocebus aethiops ; Down-Regulation/drug effects ; Epithelial Cells/drug effects ; Epithelial Cells/immunology ; Epithelial Cells/virology ; HEK293 Cells ; Host Microbial Interactions/drug effects ; Host Microbial Interactions/immunology ; Humans ; In Vitro Techniques ; Lung/drug effects ; Lung/immunology ; Lung/virology ; Mice ; Mice, Inbred BALB C ; Receptors, Virus/antagonists & inhibitors ; Receptors, Virus/immunology ; SARS-CoV-2/immunology ; Serine Endopeptidases/drug effects ; Serine Endopeptidases/genetics ; Serine Endopeptidases/immunology ; Transcription, Genetic/drug effects ; Transcription, Genetic/immunology ; Vero Cells
    Chemical Substances Adjuvants, Immunologic ; Broncho-Vaxom ; Cell Extracts ; Receptors, Virus ; Ace2 protein, mouse (EC 3.4.17.23) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) ; Serine Endopeptidases (EC 3.4.21.-) ; TMPRSS2 protein, mouse (EC 3.4.21.-)
    Language English
    Publishing date 2021-12-10
    Publishing country United States
    Document type Journal Article
    ZDB-ID 121011-7
    ISSN 1097-6825 ; 1085-8725 ; 0091-6749
    ISSN (online) 1097-6825 ; 1085-8725
    ISSN 0091-6749
    DOI 10.1016/j.jaci.2021.11.019
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

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    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
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  2. Article ; Online: Airway administration of OM-85, a bacterial lysate, blocks experimental asthma by targeting dendritic cells and the epithelium/IL-33/ILC2 axis.

    Pivniouk, Vadim / Gimenes-Junior, Joao A / Ezeh, Peace / Michael, Ashley / Pivniouk, Oksana / Hahn, Seongmin / VanLinden, Sydney R / Malone, Sean P / Abidov, Amir / Anderson, Dayna / Gozdz, Justyna / DeVries, Avery / Martinez, Fernando D / Pasquali, Christian / Vercelli, Donata

    The Journal of allergy and clinical immunology

    2021  Volume 149, Issue 3, Page(s) 943–956

    Abstract: Background: Microbial interventions against allergic asthma have robust epidemiologic underpinnings and the potential to recalibrate disease-inducing immune responses. Oral administration of OM-85, a standardized lysate of human airways bacteria, is ... ...

    Abstract Background: Microbial interventions against allergic asthma have robust epidemiologic underpinnings and the potential to recalibrate disease-inducing immune responses. Oral administration of OM-85, a standardized lysate of human airways bacteria, is widely used empirically to prevent respiratory infections and a clinical trial is testing its ability to prevent asthma in high-risk children. We previously showed that intranasal administration of microbial products from farm environments abrogates experimental allergic asthma.
    Objectives: We sought to investigate whether direct administration of OM-85 to the airway compartment protects against experimental allergic asthma; and to identify protective cellular and molecular mechanisms activated through this natural route.
    Methods: Different strains of mice sensitized and challenged with ovalbumin or Alternaria received OM-85 intranasally, and cardinal cellular and molecular asthma phenotypes were measured. Airway transfer experiments assessed whether OM-85-treated dendritic cells protect allergen-sensitized, OM-85-naive mice against asthma.
    Results: Airway OM-85 administration suppressed allergic asthma in all models acting on multiple innate and adaptive immune targets: the airway epithelium/IL-33/ILC2 axis, lung allergen-induced type 2 responses, and dendritic cells whose Myd88/Trif-dependent tolerogenic reprogramming was sufficient to transfer OM-85-induced asthma protection.
    Conclusions: We provide the first demonstration that administering a standardized bacterial lysate to the airway compartment protects from experimental allergic asthma by engaging multiple immune pathways. Because protection required a cumulative dose 27- to 46-fold lower than the one reportedly active through the oral route, the efficacy of intranasal OM-85 administration may reflect its direct access to the airway mucosal networks controlling the initiation and development of allergic asthma.
    MeSH term(s) Allergens ; Animals ; Asthma ; Cell Extracts ; Dendritic Cells ; Disease Models, Animal ; Epithelium ; Humans ; Immunity, Innate ; Interleukin-33 ; Lung ; Lymphocytes ; Mice ; Mice, Inbred BALB C ; Ovalbumin
    Chemical Substances Allergens ; Broncho-Vaxom ; Cell Extracts ; Interleukin-33 ; Ovalbumin (9006-59-1)
    Language English
    Publishing date 2021-09-22
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 121011-7
    ISSN 1097-6825 ; 1085-8725 ; 0091-6749
    ISSN (online) 1097-6825 ; 1085-8725
    ISSN 0091-6749
    DOI 10.1016/j.jaci.2021.09.013
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Uh III Zs.92: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

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