1932

Abstract

The gut-associated lymphoid tissue (GALT) faces a considerable challenge. It encounters antigens derived from an estimated 1014 commensal microbes and greater than 30 kg of food proteins yearly. It must distinguish these harmless antigens from potential pathogens and mount the appropriate host immune response. Local and systemic hyporesponsiveness to dietary antigens, classically referred to as oral tolerance, comprises a distinct complement of adaptive cellular and humoral immune responses. It is increasingly evident that a functional epithelial barrier engaged in intimate interplay with innate immune cells and the resident microbiota is critical to establishing and maintaining oral tolerance. Moreover, innate immune cells serve as a bridge between the microbiota, epithelium, and the adaptive immune system, parlaying tonic microbial stimulation into signals critical for mucosal homeostasis. Dysregulation of gut homeostasis and the subsequent disruption of tolerance therefore have clinically significant consequences for the development of food allergy.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-immunol-042718-041621
2019-04-26
2024-03-29
Loading full text...

Full text loading...

/deliver/fulltext/immunol/37/1/annurev-immunol-042718-041621.html?itemId=/content/journals/10.1146/annurev-immunol-042718-041621&mimeType=html&fmt=ahah

Literature Cited

  1. 1.
    Sicherer SH, Allen K, Lack G, Taylor SL, Donovan SM, Oria M 2017. Critical issues in food allergy: a National Academies consensus report. Pediatrics 140:e20170194
    [Google Scholar]
  2. 2.
    Iweala OI, Burks AW 2016. Food allergy: our evolving understanding of its pathogenesis, prevention, and treatment. Curr. Allergy Asthma Rep. 16:37
    [Google Scholar]
  3. 3.
    Spergel JM, Paller AS 2003. Atopic dermatitis and the atopic march. J. Allergy Clin. Immunol. 112:S118–27
    [Google Scholar]
  4. 4.
    Tordesillas L, Berin MC, Sampson HA 2017. Immunology of food allergy. Immunity 47:32–50
    [Google Scholar]
  5. 5.
    Chinthrajah RS, Hernandez JD, Boyd SD, Galli SJ, Nadeau KC 2016. Molecular and cellular mechanisms of food allergy and food tolerance. J. Allergy Clin. Immunol. 137:984–97
    [Google Scholar]
  6. 6.
    Strachan DP 1989. Hay fever, hygiene, and household size. Br. Med. J. 299:1259–60
    [Google Scholar]
  7. 7.
    Prioult G, Nagler-Anderson C 2005. Mucosal immunity and allergic responses: lack of regulation and/or lack of microbial stimulation?. Immunol. Rev. 206:204–18
    [Google Scholar]
  8. 8.
    Noverr MC, Huffnagle GB 2005. The ‘microflora hypothesis’ of allergic diseases. Clin. Exp. Allergy 35:1511–20
    [Google Scholar]
  9. 9.
    Rook GA 2010. 99th Dahlem conference on infection, inflammation and chronic inflammatory disorders: Darwinian medicine and the ‘hygiene’ or ‘old friends’ hypothesis. Clin. Exp. Immunol. 160:70–79
    [Google Scholar]
  10. 10.
    Rook GA, Lowry CA, Raison CL 2013. Microbial ‘Old Friends’, immunoregulation and stress resilience. Evol. Med. Public Health 2013:46–64
    [Google Scholar]
  11. 11.
    Hanski I, von Hertzen L, Fyhrquist N, Koskinen K, Torppa K et al. 2012. Environmental biodiversity, human microbiota, and allergy are interrelated. PNAS 109:8334–39
    [Google Scholar]
  12. 12.
    Wypych TP, Marsland BJ 2018. Antibiotics as instigators of microbial dysbiosis: implications for asthma and allergy. Trends Immunol 39:697–711
    [Google Scholar]
  13. 13.
    Lambrecht BN, Hammad H 2017. The immunology of the allergy epidemic and the hygiene hypothesis. Nat. Immunol. 18:1076–83
    [Google Scholar]
  14. 14.
    De Filippo C, Cavalieri D, Di Paola M, Ramazzotti M, Poullet JB et al. 2010. Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa. PNAS 107:14691–96
    [Google Scholar]
  15. 15.
    David LA, Maurice CF, Carmody RN, Gootenberg DB, Button JE et al. 2014. Diet rapidly and reproducibly alters the human gut microbiome. Nature 505:559–63
    [Google Scholar]
  16. 16.
    Maizels RM, McSorley HJ 2016. Regulation of the host immune system by helminth parasites. J. Allergy Clin. Immunol. 138:666–75
    [Google Scholar]
  17. 17.
    Ober C, Sperling AI, von Mutius E, Vercelli D 2017. Immune development and environment: lessons from Amish and Hutterite children. Curr. Opin. Immunol. 48:51–60
    [Google Scholar]
  18. 18.
    Lack G 2008. Epidemiologic risks for food allergy. J. Allergy Clin. Immunol. 121:1331–36
    [Google Scholar]
  19. 19.
    Wesemann DR, Nagler CR 2016. The microbiome, timing, and barrier function in the context of allergic disease. Immunity 44:728–38
    [Google Scholar]
  20. 20.
    Feehley T, Stefka AT, Cao S, Nagler CR 2012. Microbial regulation of allergic responses to food. Semin. Immunopathol. 34:671–88
    [Google Scholar]
  21. 21.
    Pabst O, Mowat AM 2012. Oral tolerance to food protein. Mucosal Immunol 5:232–39
    [Google Scholar]
  22. 22.
    Kraehenbuhl J-P, Neutra MR 2000. Epithelial M cells: differentiation and function. Annu. Rev. Cell Dev. Biol. 16:301–32
    [Google Scholar]
  23. 23.
    Mabbott NA, Donaldson DS, Ohno H, Williams IR, Mahajan A 2013. Microfold (M) cells: important immunosurveillance posts in the intestinal epithelium. Mucosal Immunol 6:666–77
    [Google Scholar]
  24. 24.
    McDole JR, Wheeler LW, McDonald KG, Wang B, Konjufca V et al. 2012. Goblet cells deliver luminal antigen to CD103+ dendritic cells in the small intestine. Nature 483:345–49
    [Google Scholar]
  25. 25.
    Knoop KA, McDonald KG, McCrate S, McDole JR, Newberry RD 2015. Microbial sensing by goblet cells controls immune surveillance of luminal antigens in the colon. Mucosal Immunol 8:198–210
    [Google Scholar]
  26. 26.
    Bonnardel J, Da Silva C, Wagner C, Bonifay R, Chasson L et al. 2017. Distribution, location, and transcriptional profile of Peyer's patch conventional DC subsets at steady state and under TLR7 ligand stimulation. Mucosal Immunol 10:1412–30
    [Google Scholar]
  27. 27.
    Sun CM, Hall JA, Blank RB, Bouladoux N, Oukka M et al. 2007. Small intestine lamina propria dendritic cells promote de novo generation of Foxp3 T reg cells via retinoic acid. J. Exp. Med. 204:1775–85
    [Google Scholar]
  28. 28.
    Benson MJ, Pino-Lagos K, Rosemblatt M, Noelle RJ 2007. All-trans retinoic acid mediates enhanced T reg cell growth, differentiation, and gut homing in the face of high levels of co-stimulation. J. Exp. Med. 204:1765–74
    [Google Scholar]
  29. 29.
    Coombes JL, Siddiqui KR, Arancibia-Carcamo CV, Hall J, Sun CM et al. 2007. A functionally specialized population of mucosal CD103+ DCs induces Foxp3+ regulatory T cells via a TGF-beta and retinoic acid-dependent mechanism. J. Exp. Med. 204:1757–64
    [Google Scholar]
  30. 30.
    Johansson-Lindbom B, Svensson M, Wurbel MA, Malissen B, Marquez G, Agace W 2003. Selective generation of gut tropic T cells in gut-associated lymphoid tissue (GALT): requirement for GALT dendritic cells and adjuvant. J. Exp. Med. 198:963–69
    [Google Scholar]
  31. 31.
    Hadis U, Wahl B, Schulz O, Hardtke-Wolenski M, Schippers A et al. 2011. Intestinal tolerance requires gut homing and expansion of FoxP3+ regulatory T cells in the lamina propria. Immunity 34:237–46
    [Google Scholar]
  32. 32.
    Rescigno M, Urbano M, Valzasina B, Francolini M, Rotta G et al. 2001. Dendritic cells express tight junction proteins and penetrate gut epithelial monolayers to sample bacteria. Nat. Immunol. 2:361–67
    [Google Scholar]
  33. 33.
    Niess JH, Brand S, Gu X, Landsman L, Jung S et al. 2005. CX3CR1-mediated dendritic cell access to the intestinal lumen and bacterial clearance. Science 307:254–58
    [Google Scholar]
  34. 34.
    Chieppa M, Rescigno M, Huang AY, Germain RN 2006. Dynamic imaging of dendritic cell extension into the small bowel lumen in response to epithelial cell TLR engagement. J. Exp. Med. 203:2841–52
    [Google Scholar]
  35. 35.
    Kim M, Galan C, Hill AA, Wu WJ, Fehlner-Peach H et al. 2018. Critical role for the microbiota in CX3CR1+ intestinal mononuclear phagocyte regulation of intestinal T cell responses. Immunity 49:151–63.e5
    [Google Scholar]
  36. 36.
    Mazzini E, Massimiliano L, Penna G, Rescigno M 2014. Oral tolerance can be established via gap junction transfer of fed antigens from CX3CR1+ macrophages to CD103+ dendritic cells. Immunity 40:248–61
    [Google Scholar]
  37. 37.
    Iliev ID, Mileti E, Matteoli G, Chieppa M, Rescigno M 2009. Intestinal epithelial cells promote colitis-protective regulatory T-cell differentiation through dendritic cell conditioning. Mucosal Immunol 2:340–50
    [Google Scholar]
  38. 38.
    Molenaar R, Greuter M, van der Marel AP, Roozendaal R, Martin SF et al. 2009. Lymph node stromal cells support dendritic cell-induced gut-homing of T cells. J. Immunol. 183:6395–402
    [Google Scholar]
  39. 39.
    Cording S, Wahl B, Kulkarni D, Chopra H, Pezoldt J et al. 2014. The intestinal micro-environment imprints stromal cells to promote efficient Treg induction in gut-draining lymph nodes. Mucosal Immunol 7:359–68
    [Google Scholar]
  40. 40.
    Cassani B, Villablanca EJ, Quintana FJ, Love PE, Lacy-Hulbert A et al. 2011. Gut-tropic T cells that express integrin α4β7 and CCR9 are required for induction of oral immune tolerance in mice. Gastroenterology 141:2109–18
    [Google Scholar]
  41. 41.
    Esterhazy D, Loschko J, London M, Jove V, Oliveira TY, Mucida D 2016. Classical dendritic cells are required for dietary antigen-mediated induction of peripheral Treg cells and tolerance. Nat. Immunol. 17:545–55
    [Google Scholar]
  42. 42.
    Nagler-Anderson C 2001. Man the barrier! Strategic defenses in the intestinal mucosa. Nat. Rev. Immunol. 1:59–67
    [Google Scholar]
  43. 43.
    Agace WW, McCoy KD 2017. Regionalized development and maintenance of the intestinal adaptive immune landscape. Immunity 46:532–48
    [Google Scholar]
  44. 44.
    Bauche D, Marie JC 2017. Transforming growth factor beta: a master regulator of the gut microbiota and immune cell interactions. Clin. Transl. Immunol. 6:e136
    [Google Scholar]
  45. 45.
    Worthington JJ, Kelly A, Smedley C, Bauche D, Campbell S et al. 2015. Integrin αvβ8-mediated TGF-β activation by effector regulatory T cells is essential for suppression of T-cell-mediated inflammation. Immunity 42:903–15
    [Google Scholar]
  46. 46.
    Boucard-Jourdin M, Kugler D, Endale Ahanda ML, This S, De Calisto J et al. 2016. β8 integrin expression and activation of TGF-β by intestinal dendritic cells are determined by both tissue microenvironment and cell lineage. J. Immunol. 197:1968–78
    [Google Scholar]
  47. 47.
    Bhattacharya N, Yuan R, Prestwood TR, Penny HL, DiMaio MA et al. 2016. Normalizing microbiota-induced retinoic acid deficiency stimulates protective CD8+ T cell-mediated immunity in colorectal cancer. Immunity 45:641–55
    [Google Scholar]
  48. 48.
    Matteoli G, Mazzini E, Iliev ID, Mileti E, Fallarino F et al. 2010. Gut CD103+ dendritic cells express indoleamine 2,3-dioxygenase which influences T regulatory/T effector cell balance and oral tolerance induction. Gut 59:595–604
    [Google Scholar]
  49. 49.
    Buyuktiryaki B, Sahiner UM, Girgin G, Birben E, Soyer OU et al. 2016. Low indoleamine 2,3-dioxygenase activity in persistent food allergy in children. Allergy 71:258–66
    [Google Scholar]
  50. 50.
    Van der Leek AP, Yanishevsky Y, Kozyrskyj AL 2017. The kynurenine pathway as a novel link between allergy and the gut microbiome. Front. Immunol 8:1374
    [Google Scholar]
  51. 51.
    Wikoff WR, Anfora AT, Liu J, Schultz PG, Lesley SA et al. 2009. Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites. PNAS 106:3698–703
    [Google Scholar]
  52. 52.
    Desbonnet L, Clarke G, Traplin A, O'Sullivan O, Crispie F et al. 2015. Gut microbiota depletion from early adolescence in mice: implications for brain and behaviour. Brain Behav. Immun. 48:165–73
    [Google Scholar]
  53. 53.
    Uto T, Takagi H, Fukaya T, Nasu J, Fukui T et al. 2018. Critical role of plasmacytoid dendritic cells in induction of oral tolerance. J. Allergy Clin. Immunol. 141:2156–67.e9
    [Google Scholar]
  54. 54.
    Tsuji M, Komatsu N, Kawamoto S, Suzuki K, Kanagawa O et al. 2009. Preferential generation of follicular B helper T cells from Foxp3+ T cells in gut Peyer's patches. Science 323:1488–92
    [Google Scholar]
  55. 55.
    Tordesillas L, Berin MC 2018. Mechanisms of oral tolerance. Clin. Rev. Allergy Immunol. 55:107–17
    [Google Scholar]
  56. 56.
    Macpherson AJ, Yilmaz B, Limenitakis JP, Ganal-Vonarburg SC 2018. IgA function in relation to the intestinal microbiota. Annu. Rev. Immunol. 36:359–81
    [Google Scholar]
  57. 57.
    Bunker JJ, Bendelac A 2018. IgA responses to microbiota. Immunity 49:211–24
    [Google Scholar]
  58. 58.
    Arpaia N, Campbell C, Fan X, Dikiy S, van der Veeken J et al. 2013. Metabolites produced by commensal bacteria promote peripheral regulatory T cell generation. Nature 504:451–55
    [Google Scholar]
  59. 59.
    Furusawa Y, Obata Y, Fukuda S, Endo TA, Nakato G et al. 2013. Commensal microbe-derived butyrate induces differentiation of colonic regulatory T cells. Nature 504:446–50
    [Google Scholar]
  60. 60.
    Sefik E, Geva-Zatorsky N, Oh S, Konnikova L, Zemmour D et al. 2015. Individual intestinal symbionts induce a distinct population of RORγ+ regulatory T cells. Science 349:993–97
    [Google Scholar]
  61. 61.
    Ohnmacht C, Park JH, Cording S, Wing JB, Atarashi K et al. 2015. The microbiota regulates type 2 immunity through RORγt+ T cells. Science 349:989–93
    [Google Scholar]
  62. 62.
    Lathrop SK, Bloom SM, Rao SM, Nutsch K, Lio CW et al. 2011. Peripheral education of the immune system by colonic commensal microbiota. Nature 478:250–54
    [Google Scholar]
  63. 63.
    Nutsch K, Chai JN, Ai TL, Russler-Germain E, Feehley T et al. 2016. Rapid and efficient generation of regulatory T cells to commensal antigens in the periphery. Cell Rep 17:206–20
    [Google Scholar]
  64. 64.
    Kim KS, Hong SW, Han D, Yi J, Jung J et al. 2016. Dietary antigens limit mucosal immunity by inducing regulatory T cells in the small intestine. Science 351:858–63
    [Google Scholar]
  65. 65.
    Peterson LW, Artis D 2014. Intestinal epithelial cells: regulators of barrier function and immune ho-meostasis. Nat. Rev. Immunol. 14:141–53
    [Google Scholar]
  66. 66.
    Strait R, Morrist SC, Finkelman FD 2004. Cytokine enhancement of anaphylaxis. Novartis Found. Symp. 257:80–91
    [Google Scholar]
  67. 67.
    Herbst T, Sichelstiel A, Schar C, Yadava K, Burki K et al. 2011. Dysregulation of allergic airway inflammation in the absence of microbial colonization. Am. J. Respir. Crit. Care Med. 184:198–205
    [Google Scholar]
  68. 68.
    Cahenzli J, Koller Y, Wyss M, Geuking MB, McCoy KD 2013. Intestinal microbial diversity during early-life colonization shapes long-term IgE levels. Cell Host Microbe 14:559–70
    [Google Scholar]
  69. 69.
    Hill DA, Siracusa MC, Abt MC, Kim BS, Kobuley D et al. 2012. Commensal bacteria-derived signals regulate basophil hematopoiesis and allergic inflammation. Nat. Med. 18:538–46
    [Google Scholar]
  70. 70.
    Hill DA, Artis D 2013. The influence of commensal bacteria-derived signals on basophil-associated allergic inflammation. Gut Microbes 4:76–83
    [Google Scholar]
  71. 71.
    Sudo N, Sawamura S-A, Tanaka K, Aiba Y, Kubo C, Koga Y 1997. The requirement of intestinal bacterial flora for the development of an IgE production system fully susceptible to oral tolerance induction. J. Immunol. 159:1739–45
    [Google Scholar]
  72. 72.
    Kiyono H, McGhee JR, Wannemuehler MJ, Michalek SM 1982. Lack of oral tolerance in C3H/HeJ mice. J. Exp. Med. 155:605–10
    [Google Scholar]
  73. 73.
    Wannemuehler MJ, Kiyono H, Babb JL, Michalek SM, McGhee JR 1982. Lipopolysaccharide (LPS) regulation of the immune response: LPS converts germfree mice to sensitivity to oral tolerance induction. J. Immunol. 129:959–65
    [Google Scholar]
  74. 74.
    Li XM, Serebrisky D, Lee SY, Huang CK, Bardina L et al. 2000. A murine model of peanut anaphylaxis: T- and B-cell responses to a major peanut allergen mimic human responses. J. Allergy Clin. Immunol. 106:150–58
    [Google Scholar]
  75. 75.
    Bashir ME, Louie S, Shi HN, Nagler-Anderson C 2004. Toll-like receptor 4 signaling by intestinal microbes influences susceptibility to food allergy. J. Immunol. 172:6978–87
    [Google Scholar]
  76. 76.
    Stefka AT, Feehley T, Tripathi P, Qiu J, McCoy K et al. 2014. Commensal bacteria protect against food allergen sensitization. PNAS 111:13145–50
    [Google Scholar]
  77. 77.
    Sabat R, Ouyang W, Wolk K 2014. Therapeutic opportunities of the IL-22-IL-22R1 system. Nat. Rev. Drug Discov. 13:21–38
    [Google Scholar]
  78. 78.
    Valenta R, Hochwallner H, Linhart B, Pahr S 2015. Food allergies: the basics. Gastroenterology 148:1120–31.e4
    [Google Scholar]
  79. 79.
    Feehley T, Belda-Ferre P, Nagler CR 2016. What's LPS got to do with it? A role for gut LPS variants in driving autoimmune and allergic disease. Cell Host Microbe 19:572–74
    [Google Scholar]
  80. 80.
    Vatanen T, Kostic AD, d'Hennezel E, Siljander H, Franzosa EA et al. 2016. Variation in microbiome LPS immunogenicity contributes to autoimmunity in humans. Cell 165:842–53 Erratum. 2016. Cell 165:1551
    [Google Scholar]
  81. 81.
    Dominguez-Bello MG, Costello EK, Contreras M, Magris M, Hidalgo G et al. 2010. Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. PNAS 107:11971–75
    [Google Scholar]
  82. 82.
    Dominguez-Bello MG, Blaser MJ, Ley RE, Knight R 2011. Development of the human gastrointestinal microbiota and insights from high-throughput sequencing. Gastroenterology 140:1713–19
    [Google Scholar]
  83. 83.
    Koenig JE, Spor A, Scalfone N, Fricker AD, Stombaugh J et al. 2011. Succession of microbial consortia in the developing infant gut microbiome. PNAS 108:Suppl. 14578–85
    [Google Scholar]
  84. 84.
    Chu DM, Ma J, Prince AL, Antony KM, Seferovic MD, Aagaard KM 2017. Maturation of the infant microbiome community structure and function across multiple body sites and in relation to mode of delivery. Nat. Med. 23:314–26
    [Google Scholar]
  85. 85.
    Mueller NT, Bakacs E, Combellick J, Grigoryan Z, Dominguez-Bello MG 2015. The infant microbiome development: mom matters. Trends Mol. Med. 21:109–17
    [Google Scholar]
  86. 86.
    Gomez de Aguero M, Ganal-Vonarburg SC, Fuhrer T, Rupp S, Uchimura Y et al. 2016. The maternal microbiota drives early postnatal innate immune development. Science 351:1296–302
    [Google Scholar]
  87. 87.
    Noval Rivas M, Burton OT, Wise P, Zhang YQ, Hobson SA et al. 2013. A microbiota signature associated with experimental food allergy promotes allergic sensitization and anaphylaxis. J. Allergy Clin. Immunol. 131:201–12
    [Google Scholar]
  88. 88.
    Ling Z, Li Z, Liu X, Cheng Y, Luo Y et al. 2014. Altered fecal microbiota composition associated with food allergy in infants. Appl. Environ. Microbiol. 80:2546–54
    [Google Scholar]
  89. 89.
    Hua X, Goedert JJ, Pu A, Yu G, Shi J 2016. Allergy associations with the adult fecal microbiota: analysis of the American Gut Project. EBioMedicine 3:172–79
    [Google Scholar]
  90. 90.
    Berni Canani R, Sangwan N, Stefka AT, Nocerino R, Paparo L et al. 2016. Lactobacillus rhamnosus GG-supplemented formula expands butyrate-producing bacterial strains in food allergic infants. ISME J 10:742–50
    [Google Scholar]
  91. 91.
    Hill C, Guarner F, Reid G, Gibson GR, Merenstein DJ et al. 2014. Expert consensus document: the International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat. Rev. Gastroenterol. Hepatol. 11:506–14
    [Google Scholar]
  92. 92.
    Berni Canani R, Nocerino R, Terrin G, Coruzzo A, Cosenza L et al. 2012. Effect of Lactobacillus GG on tolerance acquisition in infants with cow's milk allergy: a randomized trial. J. Allergy Clin. Immunol. 129:580–82
    [Google Scholar]
  93. 93.
    Berni Canani R, Nocerino R, Terrin G, Frediani T, Lucarelli S et al. 2013. Formula selection for managment of children with cow milk allergy influences the rate of acquisition of tolerance: a prospective multicenter study. J. Pediatr. 163:771–77
    [Google Scholar]
  94. 94.
    Bunyavanich S, Shen N, Grishin A, Wood R, Burks W et al. 2016. Early-life gut microbiome composition and milk allergy resolution. J. Allergy Clin. Immunol. 138:1122–30
    [Google Scholar]
  95. 95.
    Blanton LV, Charbonneau MR, Salih T, Barratt MJ, Venkatesh S et al. 2016. Gut bacteria that prevent growth impairments transmitted by microbiota from malnourished children. Science 351:aad3311
    [Google Scholar]
  96. 96.
    Feehley T, Plunkett CH, Bao R, Choi Hong SM, Culleen E et al. 2019. Healthy infants harbor intestinal bacteria that protect against food allergy. Nat. Med. 25:448–53
    [Google Scholar]
  97. 97.
    Perry TT, Conover-Walker MK, Pomes A, Chapman MD, Wood RA 2004. Distribution of peanut allergen in the environment. J. Allergy Clin. Immunol. 113:973–76
    [Google Scholar]
  98. 98.
    Brough HA, Santos AF, Makinson K, Penagos M, Stephens AC et al. 2013. Peanut protein in household dust is related to household peanut consumption and is biologically active. J. Allergy Clin. Immunol. 132:630–38
    [Google Scholar]
  99. 99.
    Matsumoto K, Saito H 2013. Epicutaneous immunity and onset of allergic diseases—per-“eczema”tous sensitization drives the allergy march. Allergol. Int. 62:291–96
    [Google Scholar]
  100. 100.
    Dioszeghy V, Mondoulet L, Dhelft V, Ligouis M, Puteaux E et al. 2011. Epicutaneous immunotherapy results in rapid allergen uptake by dendritic cells through intact skin and downregulates the allergen-specific response in sensitized mice. J. Immunol. 186:5629–37
    [Google Scholar]
  101. 101.
    Klechevsky E, Morita R, Liu M, Cao Y, Coquery S et al. 2008. Functional specializations of human epidermal Langerhans cells and CD14+ dermal dendritic cells. Immunity 29:497–510
    [Google Scholar]
  102. 102.
    Nagao K, Kobayashi T, Moro K, Ohyama M, Adachi T et al. 2012. Stress-induced production of chemokines by hair follicles regulates the trafficking of dendritic cells in skin. Nat. Immunol. 13:744–52
    [Google Scholar]
  103. 103.
    Tomura M, Honda T, Tanizaki H, Otsuka A, Egawa G et al. 2010. Activated regulatory T cells are the major T cell type emigrating from the skin during a cutaneous immune response in mice. J. Clin. Investig. 120:883–93
    [Google Scholar]
  104. 104.
    Majewska-Szczepanik M, Zemelka-Wiacek M, Ptak W, Wen L, Szczepanik M 2012. Epicutaneous immunization with DNP-BSA induces CD4+ CD25+ Treg cells that inhibit Tc1-mediated CS. Immunol. Cell Biol. 90:784–95
    [Google Scholar]
  105. 105.
    Hill DJ, Sporik R, Thorburn J, Hosking CS 2000. The association of atopic dermatitis in infancy with immunoglobulin E food sensitization. J. Pediatr. 137:475–79
    [Google Scholar]
  106. 106.
    Lack G, Fox D, Northstone K, Golding JAvon Longitud. Study of Parents Child. Study Team. 2003. Factors associated with the development of peanut allergy in childhood. N. Engl. J. Med 348:977–85
    [Google Scholar]
  107. 107.
    O'Regan GM, Sandilands A, McLean WHI, Irvine AD 2008. Filaggrin in atopic dermatitis. J. Allergy Clin. Immunol. 122:689–93
    [Google Scholar]
  108. 108.
    Brough HA, Simpson A, Makinson K, Hankinson J, Brown S et al. 2014. Peanut allergy: effect of environmental peanut exposure in children with filaggrin loss-of-function mutations. J. Allergy Clin. Immunol. 134:867–75.e1
    [Google Scholar]
  109. 109.
    Venkataraman D, Soto-Ramirez N, Kurukulaaratchy RJ, Holloway JW, Karmaus W et al. 2014. Filaggrin loss-of-function mutations are associated with food allergy in childhood and adolescence. J. Allergy Clin. Immunol. 134:876–82.e4
    [Google Scholar]
  110. 110.
    Mondoulet L, Dioszeghy V, Puteaux E, Ligouis M, Dhelft V et al. 2012. Intact skin and not stripped skin is crucial for the safety and efficacy of peanut epicutaneous immunotherapy (EPIT) in mice. Clin. Transl. Allergy 2:22
    [Google Scholar]
  111. 111.
    Tordesillas L, Goswami R, Benede S, Grishina G, Dunkin D et al. 2014. Skin exposure promotes a Th2-dependent sensitization to peanut allergens. J. Clin. Investig. 124:4965–75
    [Google Scholar]
  112. 112.
    Leyva-Castillo JM, Hener P, Jiang H, Li M 2013. TSLP produced by keratinocytes promotes allergen sensitization through skin and thereby triggers atopic march in mice. J. Investig. Dermatol. 133:154–63
    [Google Scholar]
  113. 113.
    Leyva-Castillo JM, Hener P, Michea P, Karasuyama H, Chan S et al. 2013. Skin thymic stromal lymphopoietin initiates Th2 responses through an orchestrated immune cascade. Nat. Commun. 4:2847
    [Google Scholar]
  114. 114.
    Noti M, Kim BS, Siracusa MC, Rak GD, Kubo M et al. 2014. Exposure to food allergens through inflamed skin promotes intestinal food allergy through the thymic stromal lymphopoietin-basophil axis. J. Allergy Clin. Immunol. 133:1390–99.e6
    [Google Scholar]
  115. 115.
    Hussain M, Borcard L, Walsh KP, Pena Rodriguez M, Mueller C et al. 2018. Basophil-derived IL-4 promotes epicutaneous antigen sensitization concomitant with the development of food allergy. J. Allergy Clin. Immunol. 141:223–34.e5
    [Google Scholar]
  116. 116.
    Scharschmidt TC, Vasquez KS, Truong HA, Gearty SV, Pauli ML et al. 2015. A wave of regulatory T cells into neonatal skin mediates tolerance to commensal microbes. Immunity 43:1011–21
    [Google Scholar]
  117. 117.
    Naik S, Bouladoux N, Wilhelm C, Molloy MJ, Salcedo R et al. 2012. Compartmentalized control of skin immunity by resident commensals. Science 337:1115–19
    [Google Scholar]
  118. 118.
    Nakatsuji T, Chiang HI, Jiang SB, Nagarajan H, Zengler K, Gallo RL 2013. The microbiome extends to subepidermal compartments of normal skin. Nat. Commun. 4:1431
    [Google Scholar]
  119. 119.
    Naik S, Bouladoux N, Linehan JL, Han SJ, Harrison OJ et al. 2015. Commensal-dendritic-cell interaction specifies a unique protective skin immune signature. Nature 520:104–8
    [Google Scholar]
  120. 120.
    Jones AL, Curran-Everett D, Leung DYM 2016. Food allergy is associated with Staphylococcus aureus colonization in children with atopic dermatitis. J. Allergy Clin. Immunol. 137:1247–48.e3
    [Google Scholar]
  121. 121.
    Nakamura Y, Oscherwitz J, Cease KB, Chan SM, Munoz-Planillo R et al. 2013. Staphylococcus δ-toxin induces allergic skin disease by activating mast cells. Nature 503:397–401
    [Google Scholar]
  122. 122.
    Kong HH, Oh J, Deming C, Conlan S, Grice EA et al. 2012. Temporal shifts in the skin microbiome associated with disease flares and treatment in children with atopic dermatitis. Genome Res 22:850–59
    [Google Scholar]
  123. 123.
    Zeeuwen PL, Ederveen TH, van der Krieken DA, Niehues H, Boekhorst J et al. 2017. Gram-positive anaerobe cocci are underrepresented in the microbiome of filaggrin-deficient human skin. J. Allergy Clin. Immunol. 139:1368–71
    [Google Scholar]
  124. 124.
    Takai T, Chen X, Xie Y, Vu AT, Le TA et al. 2014. TSLP expression induced via Toll-like receptor pathways in human keratinocytes. Methods Enzymol 535:371–87
    [Google Scholar]
  125. 125.
    Wang J, Lack G 2017. Food allergy: unmet needs and new perspectives. J. Allergy Clin. Immunol. Pract. 5:295
    [Google Scholar]
  126. 126.
    Wang Z, MacLeod DT, Di Nardo A 2012. Commensal bacteria lipoteichoic acid increases skin mast cell antimicrobial activity against vaccinia viruses. J. Immunol. 189:1551–58
    [Google Scholar]
  127. 127.
    O'Shea KM, Aceves SS, Dellon ES, Gupta SK, Spergel JM et al. 2018. Pathophysiology of eosinophilic esophagitis. Gastroenterology 154:333–45
    [Google Scholar]
  128. 128.
    Davis BP, Stucke EM, Khorki ME, Litosh VA, Rymer JK et al. 2016. Eosinophilic esophagitis-linked calpain 14 is an IL-13-induced protease that mediates esophageal epithelial barrier impairment. JCI Insight 1:e86355
    [Google Scholar]
  129. 129.
    Aceves SS 2014. Food allergy testing in eosinophilic esophagitis: what the gastroenterologist needs to know. Clin. Gastroenterol. Hepatol. 12:1216–23
    [Google Scholar]
  130. 130.
    Martin LJ, He H, Collins MH, Abonia JP, Biagini Myers JM et al. 2018. Eosinophilic esophagitis (EoE) genetic susceptibility is mediated by synergistic interactions between EoE-specific and general atopic disease loci. J. Allergy Clin. Immunol. 141:1690–98
    [Google Scholar]
  131. 131.
    May M, Abrams JA 2018. Emerging insights into the esophageal microbiome. Curr. Treat. Options Gastroenterol. 16:72–85
    [Google Scholar]
  132. 132.
    Roy-Ghanta S, Larosa DF, Katzka DA 2008. Atopic characteristics of adult patients with eosinophilic esophagitis. Clin. Gastroenterol. Hepatol. 6:531–35
    [Google Scholar]
  133. 133.
    Hruz P, Straumann A, Bussmann C, Heer P, Simon HU et al. 2011. Escalating incidence of eosinophilic esophagitis: a 20-year prospective, population-based study in Olten County, Switzerland. J. Allergy Clin. Immunol. 128:1349–50.e5
    [Google Scholar]
  134. 134.
    Prasad GA, Alexander JA, Schleck CD, Zinsmeister AR, Smyrk TC et al. 2009. Epidemiology of eosinophilic esophagitis over three decades in Olmsted County, Minnesota. Clin. Gastroenterol. Hepatol. 7:1055–61
    [Google Scholar]
  135. 135.
    Dellon ES, Peery AF, Shaheen NJ, Morgan DR, Hurrell JM et al. 2011. Inverse association of esophageal eosinophilia with Helicobacter pylori based on analysis of a US pathology database. Gastroenterology 141:1586–92
    [Google Scholar]
  136. 136.
    Furuta GT, Kagalwalla AF, Lee JJ, Alumkal P, Maybruck BT et al. 2013. The oesophageal string test: A novel, minimally invasive method measures mucosal inflammation in eosinophilic oesophagitis. Gut 62:1395–405
    [Google Scholar]
  137. 137.
    Spergel JM, Book WM, Mays E, Song L, Shah SS et al. 2011. Variation in prevalence, diagnostic criteria, and initial management options for eosinophilic gastrointestinal diseases in the United States. J. Pediatr. Gastroenterol. Nutr. 52:300–6
    [Google Scholar]
  138. 138.
    Jensen ET, Kuhl JT, Martin LJ, Rothenberg ME, Dellon ES 2018. Prenatal, intrapartum and postnatal factors are associated with pediatric eosinophilic esophagitis. J. Allergy Clin. Immunol. 141:214–22
    [Google Scholar]
  139. 139.
    Gall A, Fero J, McCoy C, Claywell BC, Sanchez CA et al. 2015. Bacterial composition of the human upper gastrointestinal tract microbiome is dynamic and associated with genomic instability in a Barrett's esophagus cohort. PLOS ONE 10:e0129055
    [Google Scholar]
  140. 140.
    Fillon SA, Harris JK, Wagner BD, Kelly CJ, Stevens MJ et al. 2012. Novel device to sample the esophageal microbiome—the esophageal string test. PLOS ONE 7:e42938
    [Google Scholar]
  141. 141.
    Elliott DRF, Walker AW, O'Donovan M, Parkhill J, Fitzgerald RC 2017. A non-endoscopic device to sample the oesophageal microbiota: a case-control study. Lancet Gastroenterol. Hepatol. 2:32–42
    [Google Scholar]
  142. 142.
    Benitez AJ, Hoffmann C, Muir AB, Dods KK, Spergel JM et al. 2015. Inflammation-associated microbiota in pediatric eosinophilic esophagitis. Microbiome 3:23
    [Google Scholar]
  143. 143.
    Harris JK, Fang R, Wagner BD, Choe HN, Kelly CJ et al. 2015. Esophageal microbiome in eosinophilic esophagitis. PLOS ONE 10:e0128346
    [Google Scholar]
  144. 144.
    Maghsoudlou P, Eaton S, De Coppi P 2014. Tissue engineering of the esophagus. Semin. Pediatr. Surg. 23:127–34
    [Google Scholar]
  145. 145.
    Samuelov L, Sarig O, Harmon RM, Rapaport D, Ishida-Yamamoto A et al. 2013. Desmoglein 1 deficiency results in severe dermatitis, multiple allergies and metabolic wasting. Nat. Genet. 45:1244–48
    [Google Scholar]
  146. 146.
    Sherrill JD, Kc K, Wu D, Djukic Z, Caldwell JM et al. 2014. Desmoglein-1 regulates esophageal epithelial barrier function and immune responses in eosinophilic esophagitis. Mucosal Immunol 7:718–29
    [Google Scholar]
  147. 147.
    Azouz NP, Ynga-Durand MA, Caldwell JM, Jain A, Rochman M et al. 2018. The antiprotease SPINK7 serves as an inhibitory checkpoint for esophageal epithelial inflammatory responses. Sci. Transl. Med. 10:eaap9736
    [Google Scholar]
  148. 148.
    Lexmond WS, Neves JF, Nurko S, Olszak T, Exley MA et al. 2014. Involvement of the iNKT cell pathway is associated with early-onset eosinophilic esophagitis and response to allergen avoidance therapy. Am. J. Gastroenterol. 109:646–57
    [Google Scholar]
  149. 149.
    Olszak T, An D, Zeissig S, Vera MP, Richter J et al. 2012. Microbial exposure during early life has persistent effects on natural killer T cell function. Science 336:489–93
    [Google Scholar]
  150. 150.
    An D, Oh SF, Olszak T, Neves JF, Avci FY et al. 2014. Sphingolipids from a symbiotic microbe regulate homeostasis of host intestinal natural killer T cells. Cell 156:123–33
    [Google Scholar]
  151. 151.
    Commins SP, Satinover SM, Hosen J, Mozena J, Borish L et al. 2009. Delayed anaphylaxis, angioedema, or urticaria after consumption of red meat in patients with IgE antibodies specific for galactose-alpha-1,3-galactose. J. Allergy Clin. Immunol. 123:426–33
    [Google Scholar]
  152. 152.
    Steinke JW, Pochan SL, James HR, Platts-Mills TAE, Commins SP 2016. Altered metabolic profile in patients with IgE to galactose-alpha-1,3-galactose following in vivo food challenge. J. Allergy Clin. Immunol. 138:1465–67.e8
    [Google Scholar]
  153. 153.
    Commins SP, Platts-Mills TA 2013. Tick bites and red meat allergy. Curr. Opin. Allergy Clin. Immunol. 13:354–59
    [Google Scholar]
  154. 154.
    Hashizume H, Fujiyama T, Umayahara T, Kageyama R, Walls AF, Satoh T 2018. Repeated Amblyomma testudinarium tick bites are associated with increased galactose-alpha-1,3-galactose carbohydrate IgE antibody levels: a retrospective cohort study in a single institution. J. Am. Acad. Dermatol. 78:1135–41.e3
    [Google Scholar]
  155. 155.
    Mangold A, Hercher D, Hlavin G, Liepert J, Zimmermann M et al. 2012. Anti-alpha-Gal antibody titres remain unaffected by the consumption of fermented milk containing Lactobacillus casei in healthy adults. Int. J. Food Sci. Nutr. 63:278–82
    [Google Scholar]
  156. 156.
    Hamsten C, Tran TAT, Starkhammar M, Brauner A, Commins SP et al. 2013. Red meat allergy in Sweden: association with tick sensitization and B-negative blood groups. J. Allergy Clin. Immunol. 132:1431–34
    [Google Scholar]
  157. 157.
    Galili U, Rachmilewitz EA, Peleg A, Flechner I 1984. A unique natural human IgG antibody with anti-alpha-galactosyl specificity. J. Exp. Med. 160:1519–31
    [Google Scholar]
  158. 158.
    Yilmaz B, Portugal S, Tran TM, Gozzelino R, Ramos S et al. 2014. Gut microbiota elicits a protective immune response against malaria transmission. Cell 159:1277–89
    [Google Scholar]
  159. 159.
    Richter D, Matuschka FR, Spielman A, Mahadevan L 2013. How ticks get under your skin: insertion mechanics of the feeding apparatus of Ixodes ricinus ticks. Proc. R. Soc. B 280:20131758
    [Google Scholar]
  160. 160.
    Qiu Y, Nakao R, Ohnuma A, Kawamori F, Sugimoto C 2014. Microbial population analysis of the salivary glands of ticks: a possible strategy for the surveillance of bacterial pathogens. PLOS ONE 9:e103961
    [Google Scholar]
  161. 161.
    Ponnusamy L, Gonzalez A, Van Treuren W, Weiss S, Parobek CM et al. 2014. Diversity of Rickettsiales in the microbiome of the lone star tick, Amblyomma americanum. Appl. Environ. Microbiol. 80:354–59
    [Google Scholar]
  162. 162.
    Van Treuren W, Ponnusamy L, Brinkerhoff RJ, Gonzalez A, Parobek CM et al. 2015. Variation in the microbiota of Ixodes ticks with regard to geography, species, and sex. Appl. Environ. Microbiol. 81:6200–9
    [Google Scholar]
  163. 163.
    Wilson JM, Schuyler AJ, Schroeder N, Platts-Mills TA 2017. Galactose-alpha-1,3-galactose: atypical food allergen or model IgE hypersensitivity?. Curr. Allergy Asthma Rep. 17:8
    [Google Scholar]
  164. 164.
    Wang ZK, Yang YS 2013. Upper gastrointestinal microbiota and digestive diseases. World J. Gastroenterol. 19:1541–50
    [Google Scholar]
  165. 165.
    Commins SP, Karim S 2017. Development of a novel murine model of alpha-gal meat allergy. J. Allergy Clin. Immunol. 139:AB193
    [Google Scholar]
  166. 166.
    Am. Acad. Pediatr. Comm. Nutr. 2000. Hypoallergenic infant formulas. Pediatrics 106:346–49
    [Google Scholar]
  167. 167.
    Du Toit G, Roberts G, Sayre PH, Bahson HT, Radulovic S et al. 2015. Randomized trial for peanut consumption in infants at risk for peanut allergy. N. Engl. J. Med 372:803–13 Erratum. 2016. N. Engl. J. Med. 375:398
    [Google Scholar]
  168. 168.
    Togias A, Cooper SF, Acebal JD, Assa'ad A, Baker JR Jr. et al. 2017. Addendum guidelines for the prevention of peanut allergy in the United States: Report of the National Institute of Allergy and Infectious Disease—sponsored expert panel. Ann. Allergy Asthma Immunol. 118:166–73
    [Google Scholar]
  169. 169.
    Virkud YV, Wang J, Shreffler WG 2018. Enhancing the safety and efficacy of food allergy immunotherapy: a review of adjunctive therapies. Clin. Rev. Allergy Immunol. 55:172–89
    [Google Scholar]
  170. 170.
    PALISADE Group Clin. Investig. Vickery BP, Vereda A, Casale TB, Beyer K et al. 2018. AR101 oral immunotherapy for peanut allergy. N. Engl. J. Med. 379:1991–2001
    [Google Scholar]
  171. 171.
    Varshney P, Steele PH, Vickery BP, Bird JA, Thyagarajan A et al. 2009. Adverse reactions during peanut oral immunotherapy home dosing. J. Allergy Clin. Immunol. 124:1351–52
    [Google Scholar]
  172. 172.
    Lucendo AJ, Arias A, Tenias JM 2014. Relation between eosinophilic esophagitis and oral immunotherapy for food allergy: a systematic review with meta-analysis. Ann. Allergy Asthma Immunol. 113:624–29
    [Google Scholar]
  173. 173.
    Leung DY, Sampson HA, Yunginger JW, Burks AW Jr., Schneider LC et al. 2003. Effect of anti-IgE therapy in patients with peanut allergy. N. Engl. J. Med. 348:986–93
    [Google Scholar]
  174. 174.
    Nadeau KC 2015. Multi Immunotherapy to Test Tolerance and Xolair (M-TAX) Study Rec. NCT02626611. https://clinicaltrials.gov/ct2/show/NCT02626611
  175. 175.
    Li X-M 2016. E-B-FAHF-2, Multi OIT and Xolair (Omalizumab) for Food Allergy Study Rec. NCT02879006. https://clinicaltrials.gov/ct2/show/NCT02879006
  176. 176.
    Nadeau KC 2015. Study Using Xolair in Rush Multi Oral Immunotherapy in Multi Food Allergic Patients (MAP-X) Study Rec. NCT02643862. https://clinicaltrials.gov/ct2/show/NCT02643862
  177. 177.
    Andorf S, Purington N, Block WM, Long AJ, Tupa D et al. 2018. Anti-IgE treatment with oral immunotherapy in multifood allergic participants: a double-blind, randomised, controlled trial. Lancet Gastroenterol. Hepatol. 3:85–94
    [Google Scholar]
  178. 178.
    Arrieta MC, Stiemsma LT, Dimitriu PA, Thorson L, Russell S et al. 2015. Early infancy microbial and metabolic alterations affect risk of childhood asthma. Sci. Transl. Med. 7:307ra152
    [Google Scholar]
  179. 179.
    Fujimura KE, Sitarik AR, Havstad S, Lin DL, Levan S et al. 2016. Neonatal gut microbiota associates with childhood multisensitized atopy and T cell differentiation. Nat. Med. 22:1187–91
    [Google Scholar]
  180. 180.
    Olle B 2013. Medicines from microbiota. Nat. Biotechnol. 31:309–15
    [Google Scholar]
  181. 181.
    Tan J, McKenzie C, Vuillermin PJ, Goverse G, Vinuesa CG et al. 2016. Dietary fiber and bacterial SCFA enhance oral tolerance and protect against food allergy through diverse cellular pathways. Cell Rep 15:2809–24
    [Google Scholar]
  182. 182.
    Tan J, McKenzie C, Potamitis M, Thorburn AN, Mackay CR, Macia L 2014. The role of short-chain fatty acids in health and disease. Adv. Immunol. 121:91–119
    [Google Scholar]
  183. 183.
    Donohoe DR, Garge N, Zhang X, Sun W, O'Connell TM et al. 2011. The microbiome and butyrate regulate energy metabolism and autophagy in the mammalian colon. Cell Metab 13:517–26
    [Google Scholar]
  184. 184.
    Byndloss MX, Olsan EE, Rivera-Chavez F, Tiffany CR, Cevallos SA et al. 2017. Microbiota-activated PPAR-gamma signaling inhibits dysbiotic Enterobacteriaceae expansion. Science 357:570–75
    [Google Scholar]
/content/journals/10.1146/annurev-immunol-042718-041621
Loading
/content/journals/10.1146/annurev-immunol-042718-041621
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error