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  1. 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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  2. 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

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  3. 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

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  4. Article: Cortisol circadian rhythms and stress responses in infants at risk of allergic disease.

    Ball, Thomas M / Anderson, Dayna / Minto, Jacqueline / Halonen, Marilyn

    The Journal of allergy and clinical immunology

    2006  Volume 117, Issue 2, Page(s) 306–311

    Abstract: Background: The cortisol circadian rhythm and response to stressful stimuli are altered in children and adults with allergic disease, including asthma. It is not known whether these alterations precede or follow the onset of allergic disease.: ... ...

    Abstract Background: The cortisol circadian rhythm and response to stressful stimuli are altered in children and adults with allergic disease, including asthma. It is not known whether these alterations precede or follow the onset of allergic disease.
    Objective: We sought to evaluate the cortisol circadian rhythm and stress response among infants at risk for the development of allergic disease.
    Methods: Infants with and without risk factors for allergic disease were evaluated at age 6 months. Saliva was obtained at 8 am, 2 pm, and 8 pm at home (n = 68) by parents when their infants were comfortable and in the clinic (n = 88) before and after their physical examination and vaccinations. Information regarding parental allergy and exposure to other children at home or in child care were obtained by questionnaire.
    Results: In multivariate analysis the circadian rhythm of cortisol was flattened because of the lack of the expected morning surge of cortisol, resulting in decreased diurnal variation of cortisol in infants of mothers with allergy (P = .035) or asthma (P = .002) or an asthmatic father (P = .022). The cortisol stress response was greater in infants of mothers with allergy (P = .045) or asthma (P = .039), those with fewer siblings (P = .066), and those not entering day care early in life (P = .017).
    Conclusions: These alterations in both basal and stress levels of endogenous cortisol among infants predisposed to allergic disease might affect the development of allergic immune responses early in life through interactions with inflammatory mediators.
    MeSH term(s) Circadian Rhythm ; Female ; Humans ; Hydrocortisone/analysis ; Hypersensitivity, Immediate/physiopathology ; Hypersensitivity, Immediate/psychology ; Hypothalamo-Hypophyseal System/physiopathology ; Infant ; Male ; Physical Examination ; Pituitary-Adrenal System/physiopathology ; Risk Factors ; Saliva/chemistry ; Stress, Psychological ; Vaccination
    Chemical Substances Hydrocortisone (WI4X0X7BPJ)
    Language English
    Publishing date 2006-02
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 121011-7
    ISSN 1085-8725 ; 1097-6825 ; 0091-6749
    ISSN (online) 1085-8725 ; 1097-6825
    ISSN 0091-6749
    DOI 10.1016/j.jaci.2005.11.009
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Adaptive cytokine production in early life differentially predicts total IgE levels and asthma through age 5 years.

    Rothers, Janet / Halonen, Marilyn / Stern, Debra A / Lohman, I Carla / Mobley, Sara / Spangenberg, Amber / Anderson, Dayna / Wright, Anne L

    The Journal of allergy and clinical immunology

    2011  Volume 128, Issue 2, Page(s) 397–402.e2

    Abstract: Background: Although it has been postulated that allergic disease is associated with a predominance of T(H)2 cells, whether IgE levels and asthma might differ in their relation to early-life cytokine production is not known.: Objective: We sought to ... ...

    Abstract Background: Although it has been postulated that allergic disease is associated with a predominance of T(H)2 cells, whether IgE levels and asthma might differ in their relation to early-life cytokine production is not known.
    Objective: We sought to assess the relationship between first-year adaptive immune cytokine production with asthma and total IgE levels through age 5 years in a nonselected birth cohort.
    Methods: Mitogen (concanavalin A/phorbol 12-myristate 13-acetate)-stimulated IL-4, IL-5, IL-13, and IFN-γ levels were measured in supernatants from cord blood mononuclear cells and PBMCs at birth, 3 months, and 12 months. Total serum IgE levels and physician-diagnosed active asthma were assessed at 1, 2, 3, and 5 years. Longitudinal models that adjust for both T(H)1 and T(H)2 cytokine production were used to determine relations of outcomes.
    Results: Relations of cytokines to total IgE levels and asthma were strikingly different. Total IgE levels through age 5 years were positively associated with 12-month IL-4 (P < .001), IL-5 (P < .001), and IL-13 (P = .02) levels when adjusted for IFN-γ levels and inversely associated with 12-month IFN-γ levels after IL-4 adjustment (P = .01). Active asthma through age 5 years was positively associated with 3-month IL-13 levels adjusted for IFN-γ (odds ratio, 2.6; P < .001) and inversely associated with 3-month IFN-γ levels adjusted for IL-13 (odds ratio, 0.5; P = .001). These relations were strongest for nonatopic asthma.
    Conclusion: Total IgE levels and active asthma through age 5 years are associated with adaptive cytokine production in early life, although relations vary temporally and with regard to the relative importance of individual cytokines.
    MeSH term(s) Adaptive Immunity/immunology ; Allergens/immunology ; Asthma/immunology ; Asthma/metabolism ; Child, Preschool ; Cohort Studies ; Cytokines/biosynthesis ; Humans ; Hypersensitivity, Immediate/immunology ; Immunoglobulin E/blood ; Infant ; Infant, Newborn ; Th1 Cells/immunology ; Th2 Cells/immunology
    Chemical Substances Allergens ; Cytokines ; Immunoglobulin E (37341-29-0)
    Language English
    Publishing date 2011-06-16
    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.2011.04.044
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Adaptive cytokine production in early life differentially predicts total IgE levels and asthma through age 5 years

    Rothers, Janet / Halonen, Marilyn / Stern, Debra A / Lohman, I. Carla / Mobley, Sara / Spangenberg, Amber / Anderson, Dayna / Wright, Anne L

    The Journal of Allergy and Clinical Immunology. 2011 Aug., v. 128, no. 2

    2011  

    Abstract: BACKGROUND: Although it has been postulated that allergic disease is associated with a predominance of TH2 cells, whether IgE levels and asthma might differ in their relation to early-life cytokine production is not known. OBJECTIVE: We sought to assess ... ...

    Abstract BACKGROUND: Although it has been postulated that allergic disease is associated with a predominance of TH2 cells, whether IgE levels and asthma might differ in their relation to early-life cytokine production is not known. OBJECTIVE: We sought to assess the relationship between first-year adaptive immune cytokine production with asthma and total IgE levels through age 5 years in a nonselected birth cohort. METHODS: Mitogen (concanavalin A/phorbol 12-myristate 13-acetate)–stimulated IL-4, IL-5, IL-13, and IFN-γ levels were measured in supernatants from cord blood mononuclear cells and PBMCs at birth, 3 months, and 12 months. Total serum IgE levels and physician-diagnosed active asthma were assessed at 1, 2, 3, and 5 years. Longitudinal models that adjust for both TH1 and TH2 cytokine production were used to determine relations of outcomes. RESULTS: Relations of cytokines to total IgE levels and asthma were strikingly different. Total IgE levels through age 5 years were positively associated with 12-month IL-4 (P < .001), IL-5 (P < .001), and IL-13 (P = .02) levels when adjusted for IFN-γ levels and inversely associated with 12-month IFN-γ levels after IL-4 adjustment (P = .01). Active asthma through age 5 years was positively associated with 3-month IL-13 levels adjusted for IFN-γ (odds ratio, 2.6; P < .001) and inversely associated with 3-month IFN-γ levels adjusted for IL-13 (odds ratio, 0.5; P = .001). These relations were strongest for nonatopic asthma. CONCLUSION: Total IgE levels and active asthma through age 5 years are associated with adaptive cytokine production in early life, although relations vary temporally and with regard to the relative importance of individual cytokines.
    Keywords asthma ; blood serum ; concanavalin A ; immunoglobulin E ; interferon-gamma ; interleukin-13 ; interleukin-4 ; interleukin-5 ; models ; mononuclear leukocytes ; odds ratio
    Language English
    Dates of publication 2011-08
    Size p. 397-402.e2.
    Publishing place Mosby, Inc.
    Document type Article
    ZDB-ID 121011-7
    ISSN 1085-8725 ; 1097-6825 ; 0091-6749
    ISSN (online) 1085-8725 ; 1097-6825
    ISSN 0091-6749
    DOI 10.1016/j.jaci.2011.04.044
    Database NAL-Catalogue (AGRICOLA)

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  7. Article ; Online: Th1/Th2 patterns and balance in cytokine production in the parents and infants of a large birth cohort.

    Halonen, Marilyn / Lohman, I Carla / Stern, Debra A / Spangenberg, Amber / Anderson, Dayna / Mobley, Sara / Ciano, Kathy / Peck, Michael / Wright, Anne L

    Journal of immunology (Baltimore, Md. : 1950)

    2009  Volume 182, Issue 5, Page(s) 3285–3293

    Abstract: Regulation of human immune cell cytokine production in vivo is not well understood due in part to limitations on imposing experimental conditions. We proposed that life-imposed conditions (pregnancy, birth, age, gender), combined with large sample size, ... ...

    Abstract Regulation of human immune cell cytokine production in vivo is not well understood due in part to limitations on imposing experimental conditions. We proposed that life-imposed conditions (pregnancy, birth, age, gender), combined with large sample size, repeat sampling, and family-based recruitment would serve to reveal peripheral blood cell-derived cytokine patterns reflective of in vivo regulation regarding Th1/Th2 balance and familial correlation. Mononuclear cells were obtained from 483 trios in the Tucson Infant Immune Study: from mothers pre- and postpartum, infants at birth and at 3 mo, and fathers. Con A/PMA-stimulated supernatants were assayed by ELISA for IFN-gamma, IL-4, IL-13, IL-5, and IL-10 and allergen-stimulated supernatants for IFN-gamma, IL-4, and IL-13. Mitogen-stimulated prepartum samples were not globally Th2 biased, differing from postpartum only by a modestly reduced IFN-gamma:IL-5 ratio. Prepartum samples actually produced less IL-10 and IL-13 although more IL-5 than paternal samples. Newborns were also not globally Th2 biased, with mitogen stimulation producing approximately 10-fold less IL-4, IL-5, and IFN-gamma than adults but only 2- to 3-fold less IL-13 and IL-10. Despite these group differences, all cytokines showed marked positive intraindividual correlations (all p < 0.001). Allergen stimulation gave results consistent with a lack of global Th2 bias. Mitogen stimulation revealed parent-child and parent-parent correlations. Thus, rather than a global Th2 bias, cytokine production in pregnant mothers and newborns appears regulated so as to maintain a relative balance among the cytokines, with the nature of the balance differing in mothers and infants and with production influenced by familial factors that include shared environment.
    MeSH term(s) Adult ; Allergens/physiology ; Asthma/diagnosis ; Asthma/immunology ; Asthma/metabolism ; Cells, Cultured ; Cohort Studies ; Cytokines/biosynthesis ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Parents ; Pregnancy ; Prospective Studies ; Rhinitis, Allergic, Seasonal/diagnosis ; Rhinitis, Allergic, Seasonal/immunology ; Rhinitis, Allergic, Seasonal/metabolism ; Risk Factors ; Th1 Cells/immunology ; Th1 Cells/metabolism ; Th2 Cells/immunology ; Th2 Cells/metabolism
    Chemical Substances Allergens ; Cytokines
    Language English
    Publishing date 2009-02-20
    Publishing country United States
    Document type Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 3056-9
    ISSN 1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
    ISSN (online) 1550-6606
    ISSN 0022-1767 ; 1048-3233 ; 1047-7381
    DOI 10.4049/jimmunol.0711996
    Database MEDical Literature Analysis and Retrieval System OnLINE

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