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  1. Article ; Online: Innate Immunity and Asthma Risk.

    Gozdz, Justyna / Ober, Carole / Vercelli, Donata

    The New England journal of medicine

    2016  Volume 375, Issue 19, Page(s) 1898–1899

    MeSH term(s) Asthma/immunology ; Humans ; Immunity, Innate/immunology ; Risk
    Language English
    Publishing date 2016-12-01
    Publishing country United States
    Document type Letter ; Comment
    ZDB-ID 207154-x
    ISSN 1533-4406 ; 0028-4793
    ISSN (online) 1533-4406
    ISSN 0028-4793
    DOI 10.1056/NEJMc1611699
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Innate lymphoid cells in asthma: when innate immunity comes in a Th2 flavor.

    Vercelli, Donata / Gozdz, Justyna / von Mutius, Erika

    Current opinion in allergy and clinical immunology

    2014  Volume 14, Issue 1, Page(s) 29–34

    Abstract: Purpose of review: Asthma is typically considered as an immunologic Th2 cell-mediated disease, a notion that is still inspiring many therapeutic strategies. In the past years, however, an innate immune cell type has been discovered in mice that resides ... ...

    Abstract Purpose of review: Asthma is typically considered as an immunologic Th2 cell-mediated disease, a notion that is still inspiring many therapeutic strategies. In the past years, however, an innate immune cell type has been discovered in mice that resides in the mucosa and secretes the Th2 cytokines IL-13 and IL-5 in response to IL-33 and IL-25 released by a damaged epithelium. These cells [now named group 2 innate lymphoid cells (ILC2s)] are rare, systemically dispersed, long-lived, and exist in humans. Recent work shows that ILC2s are critical for the development of asthma and related phenotypes in mice. Their role in human asthma remains unknown.
    Recent findings: This article reviews the most recent work that highlights ILC2s and the mechanisms underlying their critical role in experimental asthma. We also review the results of asthma therapeutic trials that targeted IL-13 and IL-5, the products of both Th2 cells and ILC2s.
    Summary: Although the limited success of these trials is often quoted to dismiss the role of Th2 immunity as a whole, we propose that Th2 cytokines released by ILC2s may be critical for human asthma, but are not adequately neutralized because they are not readily accessible in peripheral tissues.
    MeSH term(s) Animals ; Asthma/immunology ; Clinical Trials as Topic ; Cytokines/immunology ; Humans ; Immunity, Innate ; Lymphocytes/immunology ; Mice ; Models, Animal ; Th2 Cells/immunology
    Chemical Substances Cytokines
    Language English
    Publishing date 2014-02
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2088710-3
    ISSN 1473-6322 ; 1528-4050
    ISSN (online) 1473-6322
    ISSN 1528-4050
    DOI 10.1097/ACI.0000000000000023
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: T-cell phenotypes are associated with serum IgE levels in Amish and Hutterite children.

    Hrusch, Cara L / Stein, Michelle M / Gozdz, Justyna / Holbreich, Mark / von Mutius, Erika / Vercelli, Donata / Ober, Carole / Sperling, Anne I

    The Journal of allergy and clinical immunology

    2019  Volume 144, Issue 5, Page(s) 1391–1401.e10

    Abstract: Objectives: Amish children raised on traditional farms have lower atopy and asthma risk than Hutterite children raised on modern farms. In our previous study we established that the Amish environment affects the innate immune response to decrease asthma ...

    Abstract Objectives: Amish children raised on traditional farms have lower atopy and asthma risk than Hutterite children raised on modern farms. In our previous study we established that the Amish environment affects the innate immune response to decrease asthma and atopy risk. Here we investigated T-cell phenotypes in the same Amish and Hutterite children as in our earlier study to elucidate how this altered innate immunity affects adaptive T cells.
    Methods: Blood was collected from 30 Amish and 30 Hutterite age- and sex-matched children; cells were cryopreserved until analysis. Flow cytometry was used to analyze cell subsets. Atopy was determined based on allergen-specific and total IgE levels.
    Results: Children exposed to Amish farms had increased activated regulatory CD4
    Conclusion: Amish children's blood leukocytes are not only altered in their innate immune status but also have distinct T-cell phenotypes that are often associated with increased antigen exposure.
    MeSH term(s) Adaptive Immunity ; Adolescent ; Allergens/immunology ; Amish ; Cells, Cultured ; Child ; Environmental Exposure/adverse effects ; Ethnic Groups ; Female ; Humans ; Hypersensitivity, Immediate/immunology ; Immunoglobulin E/blood ; Immunophenotyping ; Male ; Phenotype ; T-Lymphocyte Subsets/immunology ; T-Lymphocytes/immunology ; Tumor Necrosis Factor alpha-Induced Protein 3/genetics ; Tumor Necrosis Factor alpha-Induced Protein 3/metabolism
    Chemical Substances Allergens ; Immunoglobulin E (37341-29-0) ; TNFAIP3 protein, human (EC 3.4.19.12) ; Tumor Necrosis Factor alpha-Induced Protein 3 (EC 3.4.19.12)
    Language English
    Publishing date 2019-08-08
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    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.2019.07.034
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  4. Article ; Online: Asthma-protective agents in dust from traditional farm environments.

    Marques Dos Santos, Mauricius / Pivniouk, Vadim / Rankl, Bettina / Walker, Alesia / Pagani, Giulia / Hertkorn, Norbert / Schmitt-Kopplin, Philippe / Müller, Christoph / Bracher, Franz / Merl-Pham, Juliane / Hauck, Stefanie M / Schloter, Michael / Michael, Ashley N / Anderson, Dayna / Honeker, Linnea / Gozdz, Justyna / Pivniouk, Oksana / Ober, Carole / Holbreich, Mark /
    Martinez, Fernando D / Snyder, Shane A / von Mutius, Erika / Vercelli, Donata

    The Journal of allergy and clinical immunology

    2023  Volume 152, Issue 3, Page(s) 610–621

    Abstract: Background: Growing up on traditional European or US Amish dairy farms in close contact with cows and hay protects children against asthma, and airway administration of extracts from dust collected from cowsheds of those farms prevents allergic asthma ... ...

    Abstract Background: Growing up on traditional European or US Amish dairy farms in close contact with cows and hay protects children against asthma, and airway administration of extracts from dust collected from cowsheds of those farms prevents allergic asthma in mice.
    Objectives: This study sought to begin identifying farm-derived asthma-protective agents.
    Methods: Our work unfolded along 2 unbiased and independent but complementary discovery paths. Dust extracts (DEs) from protective and nonprotective farms (European and Amish cowsheds vs European sheep sheds) were analyzed by comparative nuclear magnetic resonance profiling and differential proteomics. Bioactivity-guided size fractionation focused on protective Amish cowshed DEs. Multiple in vitro and in vivo functional assays were used in both paths. Some of the proteins thus identified were characterized by in-solution and in-gel sodium dodecyl sulfate-polyacrylamide gel electrophoresis enzymatic digestion/peptide mapping followed by liquid chromatography/mass spectrometry. The cargo carried by these proteins was analyzed by untargeted liquid chromatography-high-resolution mass spectrometry.
    Results: Twelve carrier proteins of animal and plant origin, including the bovine lipocalins Bos d 2 and odorant binding protein, were enriched in DEs from protective European cowsheds. A potent asthma-protective fraction of Amish cowshed DEs (≈0.5% of the total carbon content of unfractionated extracts) contained 7 animal and plant proteins, including Bos d 2 and odorant binding protein loaded with fatty acid metabolites from plants, bacteria, and fungi.
    Conclusions: Animals and plants from traditional farms produce proteins that transport hydrophobic microbial and plant metabolites. When delivered to mucosal surfaces, these agents might regulate airway responses.
    MeSH term(s) Female ; Animals ; Cattle ; Mice ; Sheep ; Farms ; Dust/analysis ; Asthma/prevention & control ; Allergens ; Respiratory System
    Chemical Substances Dust ; Allergens
    Language English
    Publishing date 2023-06-02
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    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.2023.05.013
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. 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
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  6. Article ; Online: Amish and Hutterite Environmental Farm Products Have Opposite Effects on Experimental Models of Asthma.

    Gozdz, Justyna / Holbreich, Mark / Metwali, Nervana / Thorne, Peter S / Sperling, Anne I / Martinez, Fernando D / Ober, Carole / von Mutius, Erika / Vercelli, Donata

    Annals of the American Thoracic Society

    2016  Volume 13 Suppl 1, Page(s) S99

    Language English
    Publishing date 2016-03
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2717461-X
    ISSN 2325-6621 ; 1943-5665 ; 2325-6621
    ISSN (online) 2325-6621 ; 1943-5665
    ISSN 2325-6621
    DOI 10.1513/AnnalsATS.201509-581MG
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  7. Article ; Online: Innate Immunity and Asthma Risk in Amish and Hutterite Farm Children.

    Stein, Michelle M / Hrusch, Cara L / Gozdz, Justyna / Igartua, Catherine / Pivniouk, Vadim / Murray, Sean E / Ledford, Julie G / Marques Dos Santos, Mauricius / Anderson, Rebecca L / Metwali, Nervana / Neilson, Julia W / Maier, Raina M / Gilbert, Jack A / Holbreich, Mark / Thorne, Peter S / Martinez, Fernando D / von Mutius, Erika / Vercelli, Donata / Ober, Carole /
    Sperling, Anne I

    The New England journal of medicine

    2016  Volume 375, Issue 5, Page(s) 411–421

    Abstract: Background: The Amish and Hutterites are U.S. agricultural populations whose lifestyles are remarkably similar in many respects but whose farming practices, in particular, are distinct; the former follow traditional farming practices whereas the latter ... ...

    Abstract Background: The Amish and Hutterites are U.S. agricultural populations whose lifestyles are remarkably similar in many respects but whose farming practices, in particular, are distinct; the former follow traditional farming practices whereas the latter use industrialized farming practices. The populations also show striking disparities in the prevalence of asthma, and little is known about the immune responses underlying these disparities.
    Methods: We studied environmental exposures, genetic ancestry, and immune profiles among 60 Amish and Hutterite children, measuring levels of allergens and endotoxins and assessing the microbiome composition of indoor dust samples. Whole blood was collected to measure serum IgE levels, cytokine responses, and gene expression, and peripheral-blood leukocytes were phenotyped with flow cytometry. The effects of dust extracts obtained from Amish and Hutterite homes on immune and airway responses were assessed in a murine model of experimental allergic asthma.
    Results: Despite the similar genetic ancestries and lifestyles of Amish and Hutterite children, the prevalence of asthma and allergic sensitization was 4 and 6 times as low in the Amish, whereas median endotoxin levels in Amish house dust was 6.8 times as high. Differences in microbial composition were also observed in dust samples from Amish and Hutterite homes. Profound differences in the proportions, phenotypes, and functions of innate immune cells were also found between the two groups of children. In a mouse model of experimental allergic asthma, the intranasal instillation of dust extracts from Amish but not Hutterite homes significantly inhibited airway hyperreactivity and eosinophilia. These protective effects were abrogated in mice that were deficient in MyD88 and Trif, molecules that are critical in innate immune signaling.
    Conclusions: The results of our studies in humans and mice indicate that the Amish environment provides protection against asthma by engaging and shaping the innate immune response. (Funded by the National Institutes of Health and others.).
    MeSH term(s) Adaptor Proteins, Vesicular Transport/deficiency ; Adolescent ; Agriculture ; Animals ; Asthma/epidemiology ; Asthma/immunology ; Child ; Christianity ; Cross-Sectional Studies ; Cytokines/blood ; Disease Models, Animal ; Dust/immunology ; Environmental Exposure ; Female ; Gene Expression ; Humans ; Immunity, Innate/genetics ; Immunity, Innate/immunology ; Immunoglobulin E/blood ; Leukocyte Count ; Leukocytes/physiology ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Models, Animal ; Myeloid Differentiation Factor 88/deficiency ; Prevalence
    Chemical Substances Adaptor Proteins, Vesicular Transport ; Cytokines ; Dust ; Myd88 protein, mouse ; Myeloid Differentiation Factor 88 ; TICAM-1 protein, mouse ; Immunoglobulin E (37341-29-0)
    Language English
    Publishing date 2016-11-01
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 207154-x
    ISSN 1533-4406 ; 0028-4793
    ISSN (online) 1533-4406
    ISSN 0028-4793
    DOI 10.1056/NEJMoa1508749
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