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Animal models of allergic bronchopulmonary aspergillosis

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Abstract

Among the allergic fungi, Aspergillus fumigatus, a saprophytic mold, distributed widely in the environment is a frequently recognized etiologic agent in a number of allergic conditions. Among the different allergic diseases caused by this fungus, allergic bronchopulmonary aspergillosis (ABPA) is by far the most significant one. The immunopathogenesis of this disease is not fully understood. Although several immunomodulatory treatments are available for allergic disease, none of them are applicable or relevant or useful in fungal induced allergy. It is essential to understand the pathogenesis of the disease including the antigen induced immunoregulation and the resulting factors, such as cytokine, chemokines, pathways activating factors, inflammatory and airway remodeling factors need to be understood for intervening with appropriate treatment. Animal models are essential in understanding these features of the disease. Several models of allergic aspergillosis have been developed in recent years in various animals. However, murine models have been studied more carefully and extensively. The exposure to antigen in mice leads to allergy very similar to ABPA with high IgE, elevated peripheral blood and lung eosinophils, pulmonary inflammation, and airway hyperreactivity. The role of various cytokines and chemokines and their receptors were also studied. In addition, immunotherapy and vaccination have been attempted in recent years using the murine model of ABPA. This review covers the murine model of Aspergillus induced allergy and asthma and presented critically our current understanding of the subject and the potential application of such a model in future for developing treatment modalities.

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References

  1. Kurup VP, Apter AJ (eds.). Allergic bronchopulmonary aspergillosis. In: Immunology and allergy clinics of North America, 1998: 471–715.

  2. Summerbell RC. Taxonomy and ecology of Aspergilluss species associated with colonizing infections of the respiratory tract. In: Kurup VP, Apter AJ, eds. Immunology and Allergy Clinics of North America, 1998: 549–573.

  3. Kurup VP, Grunig G, Knutsen AP, Murali PS. Cytokines in allergic bronchopulmonary aspergillosis. 73rd Forum in Immunology 1998: 466–477.

  4. Kurup VP, Banerjee B. Allergic aspergillosis: Autigens and immunodiagnosis. In: Srivasstava OP, Srivasstava AK, Shukla P, eds. Advances in medical mycology, 1996: 133–154.

  5. Knutsen AP, Mueller KR, Hutcheson PS, Slavin GR. T-and B-cell dysregulation in cystic fibrosis patients with allergic bronchopulmonary aspergillosis. Clin Immunol Immunopathol 1990; 55: 129–138.

    Article  PubMed  CAS  Google Scholar 

  6. Knutsen AP, Chauhan B, Slavin RG Cell-mediated immunity in allergic bronchopulmonary aspergillosis. In: Kurup VP, Apter AJ eds. Imunology and allergy clinics of North America, 1998: 575–599.

  7. Kurup VP, Banerjee B, IIeminann S, Greenberger PA, Blaser K, Craineri R. Selected recombinant Aspergillus fumigatus allergens bind specifically to IgE in ABPA. Clin Exp Allergy 2000; 30: 988–993.

    Article  PubMed  CAS  Google Scholar 

  8. Greenberger PA: Allergic bronchopulmonary aspergillosis. In: Middleton E, Reed CE, Ellis EF, Adkinson NF, Yunginer JW, eds. Allergy Principle and Practice, Mosby, St. Louis, 1988: 1219–1236.

    Google Scholar 

  9. Patterson R, Greenberger PA, Halwig JM, Liotta IL, Roberts M. Allergic bronchopulmonary aspergillosis. Natural history and classification of early disease by serologic and roentgenograpbic studies. Arch Intern Med 1986; 146: 916–918.

    Article  PubMed  CAS  Google Scholar 

  10. Laufer P, Fink JN, Burns WT, Ung GFR, Challenge JH, Greenberger PA, Patterson R. Allergic bronchopulmonary aspergillosis in cystic fibrosis. J Allergy Clin Immunol 1984; 73: 44–48.

    Article  PubMed  CAS  Google Scholar 

  11. Nelson LA, Callerame ML, Schwartz RH. Aspergillosis and atopy in cystic fibrosis. Am Rev Respir Dis 1979; 120: 863–873.

    PubMed  CAS  Google Scholar 

  12. Brown JE, Greenberger PA, Yarnold PR. Soluble serum interleukin 2 receptors in patients with asthma and allergic bronchopulmonary aspergillosis. Ann Allergy Asthma Immunol 1995; 74: 484–488.

    PubMed  CAS  Google Scholar 

  13. Fink JN, Kurup VP. Allergic bronchopulmonary aspergillosis. In: Barnes PJ, Grunstein MM, Leff AR, Woolcock AJ, eds. Asthma, Lippincott-Raven, Philadelphia, 1977: 2077–2087.

    Google Scholar 

  14. Murali PS, Kurup VP, Bansal NK, Fink JN, Greenberger PA. IgE downregulation and cytokine induction by Aspergillus antigens in human allergic bronchopulmonary aspergillosis. J Lab Clin Med 1998; 131: 228–235.

    Article  PubMed  CAS  Google Scholar 

  15. Knutsen AP, Slavin RG. In vitro T cell responses in cystic fibrosis patients with allergic bronchopulmonary aspergillosis. J Lab Clin Med 1989; 113: 428–435.

    PubMed  CAS  Google Scholar 

  16. Hogaboam CM, Blease K, Mehrad B, Steinhauser ML, Standiford TJ, Kunkel SL, Lukacs NW. Chronic airway hyperreactivity goblet cell hyperplasma and peribronchial fibrosis during allergic airway disease induced by Aspergillus fumigatus. Am J Path 2000; 156: 723–732.

    PubMed  CAS  Google Scholar 

  17. Grunig G, Corry DB, Coffman RL, Rennick DM Kurup VP. Animal models of allergic bronchopulmonary aspergillosis. In: Kurup VP, Apter AJ, eds. Immunology and allergy clinics of North America, 1998: 661–679.

  18. Nagai H, Guo J, Choi H, Kump V. Interferon-γ and tumor necrosis factor-α protect mice from invasive aspergillosis. J Infect Dis 1996; 172: 1554–1560.

    Google Scholar 

  19. Cenci E, Perito S, Enssle KH, et al. Th1 and Th2 cytokines in mice with invasive aspergillosis. Infect Immun 1997; 65: 564–570.

    PubMed  CAS  Google Scholar 

  20. Kurup VP, Guo J, Murali PS, Choi H, Fink JN. ImmunopathologicaI responses to Aspergillus antigen in interleukin-4 knockout mice. J Lab Clin Med 1997; 130: 567–575.

    Article  PubMed  CAS  Google Scholar 

  21. Kurup VP, Seymour BWP, Choi H, Coffman RL. Particulate Aspergillus fumigatus antigens elicit a Th2 response in BALB/c nice. J Allergy Clin Immunol 1994; 93: 1013–1020.

    Article  PubMed  CAS  Google Scholar 

  22. Kurup VP, Choi H, Murali PS, Resnick A, Fink JN, Coffman RL. Role of particulate antigens of Aspergillus in murine eosinophilia. Int Arch Allergy Immunol 1997; 112: 270–278.

    Article  PubMed  CAS  Google Scholar 

  23. Murali PS, Bainrab BS, Cboi H, Fink IN, Kurup VP. Hyperimmune serum modulates allergic response to spores in a murine model of allergic aspergillosis. J Leukoc Biol 1994; 55: 29–34.

    PubMed  CAS  Google Scholar 

  24. Kurup VP, Mauze S, Choi HY, Seymour BWP, Coffman RL. A murine model of allergic bronchopulmonary aspergillosis with elevated eosinophils and IgE. J Immunol 1992; 148: 3783–3788.

    PubMed  CAS  Google Scholar 

  25. Wang JM, Denis M, Fournier M, et al. Experimental allergic bronchopulmonary aspergillosis in the mouse: immunological and histological features. Scand J Immunol 1994; 39: 19–26.

    Article  PubMed  CAS  Google Scholar 

  26. Kurup VP, Murali PS, Guo J, Choi H Banerjee B Fink JN, Coffman RL. Anti-IL-4 and IL-S antibodies downregulate IgE and eosinophilia in mice exposed to Aspergillus antigens. Allergy 1997; 52: 1215–1221.

    PubMed  CAS  Google Scholar 

  27. Chu HW, Wang JM, Boutet M, et al. Immunohistochemical detection of GM-CSF, IL-4 and IL-5 in a murine model of allergic bronchopulmonary aspergillosis. Clin Exp Allergy 1996; 26: 461–468.

    Article  PubMed  CAS  Google Scholar 

  28. Chu HW, Wang JM, Boutet M, et al. Increased expression of intercellular adhesion molecule-1 (ICAM-2) in a murine model of pulmonary eosinophilia and high IgE level. Clin Exp Immunol 1995; 100: 329–324.

    Google Scholar 

  29. Chu HW, Wang JM, Boutet M, et al. Tumor necrosis factoralpha and interleukin-1 alpha expression in a murine model of allergic bronchopulmonary aspergillosis. Lab Anim Sci 1996; 46: 42–47.

    PubMed  CAS  Google Scholar 

  30. Kurup VP, Ramasamy M, Greenberger PA, Fink JN. Isolation and characterization of a relevant Aspergillus fumigatus antigen with IgG-and IgE-binding activity. Int Arch Allergy Appl Immunol 1988; 86: 176–182.

    PubMed  CAS  Google Scholar 

  31. Kurup VP, Resnick A, Scribner GB, Gunersekaran M, Fink JN. Enzyme profile and immunochemical characterization of Aspergillus fumigatus antigens. J Allergy Clin Immunol 1986; 78: 1166–1173.

    Article  PubMed  CAS  Google Scholar 

  32. Tomee JF, Wierenga AT, Hiemstra PS, et al. Proteases from Aspergillus fumigatus induce release of proinflammatory cytokines and cell detachment in airway epithelial cell lines. J Infect Dis 1997; 176: 300–303.

    PubMed  CAS  Google Scholar 

  33. Amitani R, Taylor G, Elezis EN. et al. Purification and characterization of factors produced by Aspergillus fumigatus which affect human ciliated respiratory epithelium. Infect Immun 1995; 63: 3266–3271.

    PubMed  CAS  Google Scholar 

  34. Kurup VP, Choi H, Murali PS, Coffman RL. IgE and eosinophil regulation in a murine model of allergic aspergillosis. J Leukoc Biol 1994; 56: 593–598.

    PubMed  CAS  Google Scholar 

  35. Mehlhop PD, van de Rijn M, Goldberg AB, et al. Allergeninduced bronchial hyperreactivity and eosinophilic inflammation occur in the absence of IgE in a mouse model of asthma. Proc Natl Acad Sci USA 1997; 94: 1344–1349.

    Article  PubMed  CAS  Google Scholar 

  36. Corry DB, Grunig G, Hadeiba H, et al. Requirements for allergen-induced airway hyperreactivity in T-and B-celldeficient mice. Molecular Med 1998; 4: 344–355.

    Article  CAS  Google Scholar 

  37. Korsgren M, Erjefalt JS, Korsgren O, et al. Allergic eosinophil-rich inflammation develops in lungs and airways of B cell-deficient nice. J Exp Med 1997; 185: 885–892.

    Article  PubMed  CAS  Google Scholar 

  38. Hamelmann E, Vella AT, Oshiba A, et al. Allergic airway sensitization induces T cell activation but not airway hyperresponsiveness in B cell-deficient mice. Proc Natl Acad Sci USA 1997; 94: 1350–1355.

    Article  PubMed  CAS  Google Scholar 

  39. Hamelmann E, Oshiba A, Schwarze J, et al. Allergen-specific IgE and IL-5 are essential for the development of airway hyperresponsiveness. Am J Respir Cell Mol Biol 1997; 16: 674–682.

    PubMed  CAS  Google Scholar 

  40. Slavin RG, Fischer VW, Levine EA, et al. A primate model of allergic bronchopulmonary aspergillosis. Int Arch Allergy Appl Immunol 1978; 56: 325–333.

    PubMed  CAS  Google Scholar 

  41. Murali PS, Dai G, Kumar A, Fink JN, Kurup VP. Aspergillus antigen-induced eosinopbil differentiation in a murine model. Infect Immun 1992; 60: 1952–1956.

    PubMed  CAS  Google Scholar 

  42. Murali PS, Kumar A, Choi LI, Bansal NK, Fink JN, Kurup VP. Aspergillus fumigatus antigen induced eosinophilia in mice is abrogated by anti-IL-5 antibody. J Leukoc Biol 1993; 53: 264–267.

    PubMed  CAS  Google Scholar 

  43. Murali PS Kurup VP, Guo J, Fink JN. Development of bone marrow eosinophilia in mice induced by Aspergillus fumigatus antigens. Clin Immunol Immunopathol 1997; 84: 216–220.

    Article  PubMed  CAS  Google Scholar 

  44. Coffman RL, Seymour BW, Hudak S, et al. Antibody to interleukin-5 inhibits helminth-induced eosinophilia in mice. Science 1989; 245: 308–310.

    PubMed  CAS  Google Scholar 

  45. Foster PS, Hogan SP, Rainsay AJ, et al. Interleukin 5 deficiency abolishes eosinophilia, airways hyperrractivity, and lung damage in a mouse asthma model. J Exp Med 1996; 183:195–201.

    Article  Google Scholar 

  46. Gonzalo JA, Lloyd CM, Kreiner L, et al. Eosinophil recruitment to the lung in a murine model of allergic inflammation. The role of T cells, chemokines, and adhesion receptors. J Clin Invest 1996; 98: 2332–2345.

    PubMed  CAS  Google Scholar 

  47. Blease K, Mehrad B, Standiford TJ, Lukacs NW, Gosling J, Boring L, Charo IF, Kunkel SL, Hogaboam CM: Enhanced pulmonary allergic responses to Aspergillus in CCR2-/-Imice. J Immunol 2000; 165: 2603–2611.

    PubMed  CAS  Google Scholar 

  48. Blease K, Mehrad B, Standiford TJ, Lukacs NW, Kunkel SL, Chensue SW, Lu B, Gerard CJ, Hogaboam CM. Airway remodeling is absent in CCRl-/-mice during chronic fungal allergic airway disease. J Immunol 2000; 165: 1564–1572.

    PubMed  CAS  Google Scholar 

  49. Lukacs NW, Stricter RM, Warmington K, et al. Differential recruitment of leukocyte populations and alteration of airway hyperreactivity by C-C family chemokines in allergic airwav inflammation. J Immunol 1997; 158: 4398–4404.

    PubMed  CAS  Google Scholar 

  50. Mould AW, Matthaei KI, Young IG, et al. Relationship between interleukin-5 and eotaxin in regulating blood and tissue eosinophilia in mice. J Clin Invest 1997; 99: 1064–107.

    Article  PubMed  CAS  Google Scholar 

  51. Grunig G, Corry DB, Leach MW, et al. Interleukin-10 is a natural suppressor of cytokine production and inflammation in a murine model of allergic bronchopulmonary aspergillosis. J Exp Med 1997; 85: 1089–1099.

    Article  Google Scholar 

  52. Kurup VP, Choi H, Resnick A, Kalbfieisch J, Fink JN. Immunopathological response of C57BL/6 and C3H/Hen mice to Aspergillus fumigatus antigens. Int. Arch. Allergy Appl. Immunol. 1990; 91: 145–154.

    PubMed  CAS  Google Scholar 

  53. Kurup VP, Choi HY, Murali PS, Xia J-Q, Coffman RL, Fink JN. Immune responses to Aspergillus antigen in IL-4-/-mice and the effect of eosinophil ablation. Allergy 1999; 54: 420–427.

    Article  PubMed  CAS  Google Scholar 

  54. Kauffman HF, Tomee JFC. Inflammatory cells and airway defense against Aspergillus fumigatus. In: Kurup VP, Apter AJ, eds. Immunology and allergy clinics of North America, 1998: 619–640.

  55. Wanner A, Salathe M, O'Riordan TG. Mucociliary clearance in the airways. Am J Resp Crit Care Med 1996; 154: 1868–1902.

    PubMed  CAS  Google Scholar 

  56. Tomee JFC, Hiemstra PS, Heinsel-Weiland R, et al. Antileukoprotease: An endogenous protein in the innate mucosal defense against fungi. J Infect Dis 1997; 176: 740–747.

    Article  PubMed  CAS  Google Scholar 

  57. Tomee JFC, Koeter GH, Kauffman HF. Secretory leukoprotease inhibitor: A native antimicrobial protein presenting new therapeutic options? Thorax 1998; 53:114–116.

    Article  PubMed  CAS  Google Scholar 

  58. Pearson AM Scavenger receptors in innate immunity. Curr Opion Immunol 1996; 8: 20–28.

    Article  CAS  Google Scholar 

  59. Mochizuki M, Bartels J, Mallet AI, Christophers E, Schroder J-M. IL-4 induces eotaxin: A possible mechanism of selective recruitment in helminth infection and atopy. J Immunol 1998; 160: 60–68.

    PubMed  CAS  Google Scholar 

  60. de Waal Malefyt R, Figdor CG, de Vries JE. Regulation of human monocyte functions by Interleukin-10. In: de Vries JE, de Waal-Malefyt R, eds. Interleukin-10, SpringerVerlag, Heidelberg, 1995: 37–52.

    Google Scholar 

  61. Blease K, Jakubzick C, Westwick J, Lukacs N, Kunkel SL, Hiogaboam CM. Therapeutic effect of IL-13 immunoneutralization during chronic experimental fungal asthma. J Immunol 2001; 166: 5219–5224.

    PubMed  CAS  Google Scholar 

  62. Ford JG, Rennick D, Donaldson DD, Venkayya R, McArthur C, Hansell E, Kurup VP, Warnock M, Grunig C. IL-13 and IFN-γ: Interactions in lung inflammation. J Immunol 2001; 167: 1769–1777.

    PubMed  CAS  Google Scholar 

  63. Hogaboam CM, Gallinat CS, Taub DD, Striter RM, Kunkel SL, Lukacs NW. Immunomodulatory role of C10 chemokine in a murine model of allergic bronchopulmonary aspergillosis. J Immunol 1999; 162: 6071–6079.

    PubMed  CAS  Google Scholar 

  64. Moser M, Crameri R, Menz G, Schneider, Dudler T, Virchow C, Gmachl M, Blaser K, Suter M. Cloning and expression of recombinant Aspergillus fumigatus allergen I/a (rAsp f 1/a) with IgE binding and type I skin test activity. J Immunol 1992; 149: 454–460.

    PubMed  CAS  Google Scholar 

  65. Arruda KL, Mann BJ, Chapman MD. Selective expression of a major allergen and cytotoxin, Asp f 1, in Aspergillus fumigatus. Implications for the immunopathogenesis of Aspergillus-related diseases. J Immunol 1992; 149: 3354–3359.

    PubMed  CAS  Google Scholar 

  66. Kumar A, Reddy LV, Sochanik A, Kurup VP. Isolation and characterization of a recombinant heat shock protein of Aspergillus fumigatus. J Allergy Clin Immunol 1993; 91: 1024–1030.

    Article  PubMed  CAS  Google Scholar 

  67. Crameri R, Blaser K. Cloning Aspergillus fumigatus allergens by the pJuFo filamentous phage display system. Int Arch Allergy Immunol 1996; 110: 41–45.

    Article  PubMed  CAS  Google Scholar 

  68. Banerjee B, Kurup VP, Phadnis S, Greenberger PA, Fink JN. Molecular cloning and expression of a recombinant Aspergillus fumigatus protein Asp f II with significant immunoglobulin IgE reactivity in allergic bronchopulmonary aspergillosis. J Lab Clin Med 1996; 127: 253–262.

    Article  PubMed  CAS  Google Scholar 

  69. Hemmann S, Blaser K, Crameri R. Allergens of Aspergillus fumigatus and Candida boidinii share IgE-binding epitopes. Am J Respir Crit Care Med 1997; 156: 1956–1960.

    PubMed  CAS  Google Scholar 

  70. Crameri R. Recombinant Aspergillus fumigatus allergens: from the nucleotide sequences to clinical applications. Eur Arch Allergy Immunol 1998; 115: 99–114.

    Article  CAS  Google Scholar 

  71. Hemmann S, Nikolaizik WH, Schöni MH, Blaser K, Crameri R. Differential IgE recognition of recombinant Aspergillus fumigatus allergens by cystic fibrosis patients with allergic bronchopulmonary aspergillosis or Aspergillus allergy. Eur J Biochem 1998; 28: 1155–1160.

    CAS  Google Scholar 

  72. Crameri R, Hemmann S, Ismail C, Menz G, Blaser K. Disease-specific recombinant allergens for the diagnosis of allergic bronchopulmonary aspergillosis. Int Immunol 1998; 10: 1211–1216.

    Article  PubMed  CAS  Google Scholar 

  73. Crameri R, Faith A, Hemmann S, Jaussi R, Ismail C, Menz G, Blaser K. Humoral and cell-mediated autoimmunity in allergy to Aspergillus fumigatus. J Exp Med 1996; 184: 265–270.

    Article  PubMed  CAS  Google Scholar 

  74. Crameri R, Jaussi R, Menz G, Blaser K. Display of expression products of eDNA libraries on phage surfaces. A versatile system for selective isolation of genes by specific gene-product/ligand interaction. Eur J Biochem 1994; 26: 53–58.

    Article  Google Scholar 

  75. Kurup VP, Xia J-Q, Crameri R, Rickaby DA, Choi HY, Fluckiger S, Blaser K, Dawson CA, Kelly KJ. Purified recombinant A. fumigatus allergens induce different responses in mice. Clin Immunol 2001; 98: 327–336.

    Article  PubMed  CAS  Google Scholar 

  76. Hoyne CF, Callow MG, Kuo MC, Thomas WR. Inhibition of T-cell responses by feeding peptides containing major and cryptic epitopes: Studies with Der p 1 allergen. Immunology 1994; 83: 190–195.

    PubMed  CAS  Google Scholar 

  77. Kurup VP, Baneijee B. Fungal allergens and peptide epitopes (review). Peptides 2000; 21: 589–599.

    Article  PubMed  CAS  Google Scholar 

  78. Svirshchevskaya E, Frolova E, Alekseeva L, Kotzareva O, Kurup VP. Intravenous injection of major and cryptic peptide epitopes of ribotoxin, Asp f 1 inhibits T eell response induced by crude Aspergillus fumigatus antigens in mice. Peptides 2000; 21: 1–8.

    Article  PubMed  CAS  Google Scholar 

  79. Tang B, Banerjee B, Greenberger PA, Fink JN, Kelly KJ, Kurup VP. Antibody binding of deletion mutants of Asp f 2, the major Aspergillus fumigatus allergen. Biochem Biophy Rec Com 2000; 270: 1128–1135.

    Article  CAS  Google Scholar 

  80. Kurup VP, Hari V, Guo J, Murali PS, Resnick A, Krishnan M, Fink JN. Aspergillus fumligatus peptides differentialIy express Th1 and Th2 cytokines. Peptides 1996; 17: 183–190.

    Article  PubMed  CAS  Google Scholar 

  81. Banerjee B, Xia J-Q, Rickaby DA, Henderson JD, Kelly KJ Fink JN, Kurup VP. Modulation of airway inflammation by immunostimulatory CpG oligodeoxy nucleotide in a murine model of allergic aspergillosis (abstract). J Allergy Clin Immunol 2001; 107: S216.

    Google Scholar 

  82. Kline JN, Waldschmidt TJ, Businga TR, Lemish JF, Weinstock JV, Thorne PS, Krieg AM.Modulation of airway inflammation by CpG oligodeoxynucleotides in a murine model of asthma. J Immunol 1998; 160: 2555–2559.

    PubMed  CAS  Google Scholar 

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  1. Allergy-Immunology Division, Medical College of Wisconsin and the Research Service, V A Medical Center, Milwaukee, WI, USA

    Viswanath P. Kurup

  2. Department of Pathology, Columbia University of Physicians and Surgeons and St. Luke's-Roosevelt Hospital, New York, NY, USA

    Gabriele Grunig

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Kurup, V.P., Grunig, G. Animal models of allergic bronchopulmonary aspergillosis. Mycopathologia 153, 165–177 (2002). https://doi.org/10.1023/A:1014963600314

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