Advertisement

Extracellular vesicle–derived protein from Bifidobacterium longum alleviates food allergy through mast cell suppression

  • Author Footnotes
    ∗ These authors contributed equally to this work.
    Jung-Hwan Kim
    Footnotes
    ∗ These authors contributed equally to this work.
    Affiliations
    Academy of Immunology and Microbiology, Institute for Basic Science, Pohang, Korea

    Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Korea
    Search for articles by this author
  • Author Footnotes
    ∗ These authors contributed equally to this work.
    Eun-Ji Jeun
    Footnotes
    ∗ These authors contributed equally to this work.
    Affiliations
    Academy of Immunology and Microbiology, Institute for Basic Science, Pohang, Korea

    Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Korea
    Search for articles by this author
  • Chun-Pyo Hong
    Affiliations
    Academy of Immunology and Microbiology, Institute for Basic Science, Pohang, Korea

    Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Korea
    Search for articles by this author
  • Seong-Hoon Kim
    Affiliations
    Division of Molecular and Life Science, Department of Life Sciences, Pohang University of Science and Technology, Pohang, Korea
    Search for articles by this author
  • Min Seong Jang
    Affiliations
    Academy of Immunology and Microbiology, Institute for Basic Science, Pohang, Korea

    Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Korea
    Search for articles by this author
  • Eun-Jung Lee
    Affiliations
    Academy of Immunology and Microbiology, Institute for Basic Science, Pohang, Korea

    Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Korea
    Search for articles by this author
  • Sook Jin Moon
    Affiliations
    Academy of Immunology and Microbiology, Institute for Basic Science, Pohang, Korea

    Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Korea
    Search for articles by this author
  • Chang Ho Yun
    Affiliations
    Academy of Immunology and Microbiology, Institute for Basic Science, Pohang, Korea
    Search for articles by this author
  • Sin-Hyeog Im
    Affiliations
    Academy of Immunology and Microbiology, Institute for Basic Science, Pohang, Korea

    Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Korea
    Search for articles by this author
  • Seok-Geun Jeong
    Affiliations
    National Institute of Animal Science, Rural Development Administration, Jeonju, Korea
    Search for articles by this author
  • Beom-Young Park
    Affiliations
    National Institute of Animal Science, Rural Development Administration, Jeonju, Korea
    Search for articles by this author
  • Kyong-Tai Kim
    Affiliations
    Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Korea

    Division of Molecular and Life Science, Department of Life Sciences, Pohang University of Science and Technology, Pohang, Korea
    Search for articles by this author
  • Ju-Young Seoh
    Affiliations
    Department of Microbiology, Ewha Womans University Graduate School of Medicine, Seoul, Korea
    Search for articles by this author
  • Yoon-Keun Kim
    Affiliations
    Department of Medicine, Ewha Womans University Graduate School of Medicine, Seoul, Korea
    Search for articles by this author
  • Sung-Jong Oh
    Affiliations
    Faculty of Biotechnology, College of Applied Life Science, Jeju National University, Jeju, Korea
    Search for articles by this author
  • Author Footnotes
    ‡ These authors contributed equally to this work.
    Jun-Sang Ham
    Correspondence
    Jun Sang Ham, PhD, National Institute of Animal Science, RDA, 1500 Kongjwipatjwi-ro, Iseo-myeon, Wanju-gun, Jeollabuk-do, Korea.
    Footnotes
    ‡ These authors contributed equally to this work.
    Affiliations
    National Institute of Animal Science, Rural Development Administration, Jeonju, Korea
    Search for articles by this author
  • Author Footnotes
    ‡ These authors contributed equally to this work.
    Bo-Gie Yang
    Correspondence
    Corresponding author: Myoung Ho Jang, PhD or Bo-Gie Yang, PhD, Academy of Immunology and Microbiology, Institute for Basic Science, 77 Cheogam-ro, Nam-gu, Pohang, Gyeongbuk 790-784, Republic of Korea.
    Footnotes
    ‡ These authors contributed equally to this work.
    Affiliations
    Academy of Immunology and Microbiology, Institute for Basic Science, Pohang, Korea
    Search for articles by this author
  • Author Footnotes
    ‡ These authors contributed equally to this work.
    Myoung Ho Jang
    Correspondence
    Corresponding author: Myoung Ho Jang, PhD or Bo-Gie Yang, PhD, Academy of Immunology and Microbiology, Institute for Basic Science, 77 Cheogam-ro, Nam-gu, Pohang, Gyeongbuk 790-784, Republic of Korea.
    Footnotes
    ‡ These authors contributed equally to this work.
    Affiliations
    Academy of Immunology and Microbiology, Institute for Basic Science, Pohang, Korea
    Search for articles by this author
  • Author Footnotes
    ∗ These authors contributed equally to this work.
    ‡ These authors contributed equally to this work.
Published:September 30, 2015DOI:https://doi.org/10.1016/j.jaci.2015.08.016

      Background

      The incidence of food allergies has increased dramatically during the last decade. Recently, probiotics have been studied for the prevention and treatment of allergic disease.

      Objective

      We examined whether Bifidobacterium longum KACC 91563 and Enterococcus faecalis KACC 91532 have the capacity to suppress food allergies.

      Methods

      B longum KACC 91563 and E faecalis KACC 91532 were administered to BALB/c wild-type mice, in which food allergy was induced by using ovalbumin and alum. Food allergy symptoms and various immune responses were assessed.

      Results

      B longum KACC 91563, but not E faecalis KACC 91532, alleviated food allergy symptoms. Extracellular vesicles of B longum KACC 91563 bound specifically to mast cells and induced apoptosis without affecting T-cell immune responses. Furthermore, injection of family 5 extracellular solute-binding protein, a main component of extracellular vesicles, into mice markedly reduced the occurrence of diarrhea in a mouse food allergy model.

      Conclusion

      B longum KACC 91563 induces apoptosis of mast cells specifically and alleviates food allergy symptoms. Accordingly, B longum KACC 91563 and family 5 extracellular solute-binding protein exhibit potential as therapeutic approaches for food allergies.

      Key words

      Abbreviations used:

      ASBP (ABC transporter, substrate-binding protein), BMMC (Bone marrow–derived mast cell), cfu (Colony-forming unit), DC (Dendritic cell), DC-SIGN (Dendritic cell–specific intercellular adhesion molecule 3–grabbing nonintegrin), ESBP (Family 5 extracellular solute-binding protein), EV (Extracellular vesicle), FISH (Fluorescence in situ hybridization), Foxp3 (Forkhead box protein 3), GST (Glutathione-S-transferase), LP (Lamina propria), MCPT-1 (Mast cell protease 1), MHCII (MHC class II), MLN (Mesenteric lymph node), OVA (Ovalbumin), TCR (T-cell receptor), TEM (Transmission electron microscopy), Treg (Regulatory T), TUNEL (In situ terminal deoxynucleotidyl transferase–mediated nick end-labeling)
      To read this article in full you will need to make a payment

      Subscribe:

      Subscribe to Journal of Allergy and Clinical Immunology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Branum A.M.
        • Lukacs S.L.
        Food allergy among children in the United States.
        Pediatrics. 2009; 124: 1549-1555
        • Sicherer S.H.
        • Sampson H.A.
        Food allergy: recent advances in pathophysiology and treatment.
        Annu Rev Med. 2009; 60: 261-277
        • Sampson H.A.
        Food allergy. Part 2: diagnosis and management.
        J Allergy Clin Immunol. 1999; 103: 981-989
        • Skolnick H.S.
        • Conover-Walker M.K.
        • Koerner C.B.
        • Sampson H.A.
        • Burks W.
        • Wood R.A.
        The natural history of peanut allergy.
        J Allergy Clin Immunol. 2001; 107: 367-374
        • Berni Canani R.
        • Nocerino R.
        • Terrin G.
        • Coruzzo A.
        • Cosenza L.
        • Leone L.
        • et al.
        Effect of Lactobacillus GG on tolerance acquisition in infants with cow's milk allergy: a randomized trial.
        J Allergy Clin Immunol. 2012; 129 (e1-5): 580-582
        • Bron P.A.
        • van Baarlen P.
        • Kleerebezem M.
        Emerging molecular insights into the interaction between probiotics and the host intestinal mucosa.
        Nat Rev Microbiol. 2012; 10: 66-78
        • Jeon S.G.
        • Kayama H.
        • Ueda Y.
        • Takahashi T.
        • Asahara T.
        • Tsuji H.
        • et al.
        Probiotic Bifidobacterium breve induces IL-10-producing Tr1 cells in the colon.
        PLoS Pathog. 2012; 8: e1002714
        • Kwon H.K.
        • Lee C.G.
        • So J.S.
        • Chae C.S.
        • Hwang J.S.
        • Sahoo A.
        • et al.
        Generation of regulatory dendritic cells and CD4+Foxp3+ T cells by probiotics administration suppresses immune disorders.
        Proc Natl Acad Sci U S A. 2010; 107: 2159-2164
        • Kawashima T.
        • Kosaka A.
        • Yan H.
        • Guo Z.
        • Uchiyama R.
        • Fukui R.
        • et al.
        Double-stranded RNA of intestinal commensal but not pathogenic bacteria triggers production of protective interferon-beta.
        Immunity. 2013; 38: 1187-1197
        • Schiavi E.
        • Barletta B.
        • Butteroni C.
        • Corinti S.
        • Boirivant M.
        • Di Felice G.
        Oral therapeutic administration of a probiotic mixture suppresses established Th2 responses and systemic anaphylaxis in a murine model of food allergy.
        Allergy. 2011; 66: 499-508
        • Thery C.
        • Ostrowski M.
        • Segura E.
        Membrane vesicles as conveyors of immune responses.
        Nat Rev Immunol. 2009; 9: 581-593
        • Kulp A.
        • Kuehn M.J.
        Biological functions and biogenesis of secreted bacterial outer membrane vesicles.
        Annu Rev Microbiol. 2010; 64: 163-184
        • Lee E.Y.
        • Choi D.Y.
        • Kim D.K.
        • Kim J.W.
        • Park J.O.
        • Kim S.
        • et al.
        Gram-positive bacteria produce membrane vesicles: proteomics-based characterization of Staphylococcus aureus-derived membrane vesicles.
        Proteomics. 2009; 9: 5425-5436
        • McBroom A.J.
        • Kuehn M.J.
        Release of outer membrane vesicles by gram-negative bacteria is a novel envelope stress response.
        Mol Microbiol. 2007; 63: 545-558
        • Rivera J.
        • Nakouzi R.J.
        • Nakouzi A.S.
        • Frases S.
        • Nicola A.
        • Casadevall A.
        Bacillus anthracis produces membrane-derived vesicles containing biologically active toxins.
        Proc Natl Acad Sci U S A. 2010; 107: 19002-19007
        • Ellis T.N.
        • Kuehn M.J.
        Virulence and immunomodulatory roles of bacterial outer membrane vesicles.
        Microbiol Mol Biol Rev. 2010; 74: 81-94
        • Lopez P.
        • Gonzalez-Rodriguez I.
        • Sanchez B.
        • Gueimonde M.
        • Margolles A.
        • Suarez A.
        Treg-inducing membrane vesicles from Bifidobacterium bifidum LMG13195 as potential adjuvants in immunotherapy.
        Vaccine. 2012; 30: 825-829
        • Kim M.R.
        • Hong S.W.
        • Choi E.B.
        • Lee W.H.
        • Kim Y.S.
        • Jeon S.G.
        • et al.
        Staphylococcus aureus-derived extracellular vesicles induce neutrophilic pulmonary inflammation via both Th1 and Th17 cell responses.
        Allergy. 2012; 67: 1271-1281
        • Kim M.K.
        • Choi A.
        • Han G.S.
        • Jeong S.G.
        • Chae H.S.
        • Jang A.
        • et al.
        Development of probiotic dairy product for the normalization of microbial flora in Korean infants.
        Korean J Food Sci Anim Resour. 2011; 31: 290-295
        • Shanahan F.
        Probiotics in perspective.
        Gastroenterology. 2010; 139: 1808-1812
        • Tam R.
        • Milton H.
        • Saier J.
        Structural, functional, and evolutionary relationships among extracellular solube-binding receptors of bacteria.
        Microbiol Rev. 1993; 57: 320-346
        • Brandt E.B.
        • Strait R.T.
        • Hershko D.
        • Wang Q.
        • Muntel E.E.
        • Scribner T.A.
        • et al.
        Mast cells are required for experimental oral allergen–induced diarrhea.
        J Clin Invest. 2003; 112: 1666-1677
        • Shin T.S.
        • Kim J.H.
        • Kim Y.S.
        • Jeon S.G.
        • Zhu Z.
        • Gho Y.S.
        • et al.
        Extracellular vesicles are key intercellular mediators in the development of immune dysfunction to allergens in the airways.
        Allergy. 2010; 65: 1256-1265
        • Uematsu S.
        • Jang M.H.
        • Chevrier N.
        • Guo Z.
        • Kumagai Y.
        • Yamamoto M.
        • et al.
        Detection of pathogenic intestinal bacteria by Toll-like receptor 5 on intestinal CD11c+ lamina propria cells.
        Nat Immunol. 2006; 7: 868-874
        • Winkler C.
        • Denker K.
        • Wortelkamp S.
        • Sickmann A.
        Silver- and Coomassie-staining protocols: detection limits and compatibility with ESI MS.
        Electrophoresis. 2007; 28: 2095-2099
        • Ham J.S.
        • Kwak W.
        • Chang O.K.
        • Han G.S.
        • Jeong S.G.
        • Seol K.H.
        • et al.
        De Novo assembly and comparative analysis of the Enterococcus faecalis genome (KACC 91532) from a Korean Neonate.
        J Microbiol Biotechnol. 2013; 23: 966-973
        • Ham J.S.
        • Lee T.
        • Byun M.J.
        • Lee K.T.
        • Kim M.K.
        • Han G.S.
        • et al.
        Complete genome sequence of Bifidobacterium longum subsp. longum KACC 91563.
        J Bacteriol. 2011; 193: 5044
        • Mathias C.B.
        • Hobson S.A.
        • Garcia-Lloret M.
        • Lawson G.
        • Poddighe D.
        • Freyschmidt E.J.
        • et al.
        IgE-mediated systemic anaphylaxis and impaired tolerance to food antigens in mice with enhanced IL-4 receptor signaling.
        J Allergy Clin Immunol. 2011; 127 (e1-6): 795-805
        • Takayama N.
        • Igarashi O.
        • Kweon M.N.
        • Kiyono H.
        Regulatory role of Peyer's patches for the inhibition of OVA-induced allergic diarrhea.
        Clin Immunol. 2007; 123: 199-208
        • Hadis U.
        • Wahl B.
        • Schulz O.
        • Hardtke-Wolenski M.
        • Schippers A.
        • Wagner N.
        • et al.
        Intestinal tolerance requires gut homing and expansion of FoxP3+ regulatory T cells in the lamina propria.
        Immunity. 2011; 34: 237-246
        • Berin M.C.
        • Mayer L.
        Immunophysiology of experimental food allergy.
        Mucosal Immunol. 2009; 2: 24-32
        • Ahrens R.
        • Osterfeld H.
        • Wu D.
        • Chen C.Y.
        • Arumugam M.
        • Groschwitz K.
        • et al.
        Intestinal mast cell levels control severity of oral antigen-induced anaphylaxis in mice.
        Am J Pathol. 2012; 180: 1535-1546
        • Fukuda S.
        • Toh H.
        • Hase K.
        • Oshima K.
        • Nakanishi Y.
        • Yoshimura K.
        • et al.
        Bifidobacteria can protect from enteropathogenic infection through production of acetate.
        Nature. 2011; 469: 543-547
        • Shen Y.
        • Giardino Torchia M.L.
        • Lawson G.W.
        • Karp C.L.
        • Ashwell J.D.
        • Mazmanian S.K.
        Outer membrane vesicles of a human commensal mediate immune regulation and disease protection.
        Cell Host Microbe. 2012; 12: 509-520
        • Atarashi K.
        • Tanoue T.
        • Oshima K.
        • Suda W.
        • Nagano Y.
        • Nishikawa H.
        • et al.
        Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota.
        Nature. 2013; 500: 232-236
        • Kalliomaki M.
        • Kirjavainen P.
        • Eerola E.
        • Kero P.
        • Salminen S.
        • Isolauri E.
        Distinct patterns of neonatal gut microflora in infants in whom atopy was and was not developing.
        J Allergy Clin Immunol. 2001; 107: 129-134
        • Wang M.
        • Karlsson C.
        • Olsson C.
        • Adlerberth I.
        • Wold A.E.
        • Strachan D.P.
        • et al.
        Reduced diversity in the early fecal microbiota of infants with atopic eczema.
        J Allergy Clin Immunol. 2008; 121: 129-134
        • Prescott S.L.
        • Bjorksten B.
        Probiotics for the prevention or treatment of allergic diseases.
        J Allergy Clin Immunol. 2007; 120: 255-262
        • Brandt E.B.
        • Munitz A.
        • Orekov T.
        • Mingler M.K.
        • McBride M.
        • Finkelman F.D.
        • et al.
        Targeting IL-4/IL-13 signaling to alleviate oral allergen-induced diarrhea.
        J Allergy Clin Immunol. 2009; 123: 53-58
        • Burton O.T.
        • Darling A.R.
        • Zhou J.S.
        • Noval-Rivas M.
        • Jones T.G.
        • Gurish M.F.
        • et al.
        Direct effects of IL-4 on mast cells drive their intestinal expansion and increase susceptibility to anaphylaxis in a murine model of food allergy.
        Mucosal Immunol. 2013; 6: 740-750
        • Smits H.H.
        • Engering A.
        • van der Kleij D.
        • de Jong E.C.
        • Schipper K.
        • van Capel T.M.
        • et al.
        Selective probiotic bacteria induce IL-10-producing regulatory T cells in vitro by modulating dendritic cell function through dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin.
        J Allergy Clin Immunol. 2005; 115: 1260-1267
        • Mashburn-Warren L.M.
        • Whiteley M.
        Special delivery: vesicle trafficking in prokaryotes.
        Mol Microbiol. 2006; 61: 839-846
        • Simpson R.J.
        • Jensen S.S.
        • Lim J.W.
        Proteomic profiling of exosomes: current perspectives.
        Proteomics. 2008; 8: 4083-4099
        • Rieu S.
        • Geminard C.
        • Rabesandratana H.
        • Sainte-Marie J.
        • Vidal M.
        Exosomes released during reticulocyte maturation bind to fibronectin via integrin alpha4beta1.
        Eur J Biochem. 2000; 267: 583-590
        • Morelli A.E.
        • Larregina A.T.
        • Shufesky W.J.
        • Sullivan M.L.
        • Stolz D.B.
        • Papworth G.D.
        • et al.
        Endocytosis, intracellular sorting, and processing of exosomes by dendritic cells.
        Blood. 2004; 104: 3257-3266
        • Konstantinov S.R.
        • Smidt H.
        • de Vos W.M.
        • Bruijns S.C.
        • Singh S.K.
        • Valence F.
        • et al.
        S layer protein A of Lactobacillus acidophilus NCFM regulates immature dendritic cell and T cell functions.
        Proc Natl Acad Sci U S A. 2008; 105: 19474-19479
        • Corr S.C.
        • Li Y.
        • Riedel C.U.
        • O'Toole P.W.
        • Hill C.
        • Gahan C.G.
        Bacteriocin production as a mechanism for the antiinfective activity of Lactobacillus salivarius UCC118.
        Proc Natl Acad Sci U S A. 2007; 104: 7617-7621
        • Ganeshan K.
        • Neilsen C.V.
        • Hadsaitong A.
        • Schleimer R.P.
        • Luo X.
        • Bryce P.J.
        Impairing oral tolerance promotes allergy and anaphylaxis: a new murine food allergy model.
        J Allergy Clin Immunol. 2009; 123: 231-238
        • Dunkin D.
        • Berin M.C.
        • Mayer L.
        Allergic sensitization can be induced via multiple physiologic routes in an adjuvant-dependent manner.
        J Allergy Clin Immunol. 2011; 128: 1251-1258