Skip to main content
SpringerLink
Log in

Pathogenesis of ABPA

  • Chapter
  • First Online:
Aspergillosis: From Diagnosis to Prevention

  • 1496 Accesses

Abstract

Aspergillus fumigatus is a ubiquitous environmental fungus, which through its size, reproductive cycle, ability to germinate at body temperature, secretion of proteases and its highly antigenic nature is an important pathogen in pulmonary disease. We will review the pathogenesis of this organism in terms of its ability to cause allergic bronchopulmonary aspergillosis (ABPA). This involves reviewing new data that examines the importance of the innate immune response to infection, especially how this limits airway colonisation and minimises the airway inflammatory response. We will also review the importance of adaptive immune responses to the organism, especially how a T helper-2 lymphocyte response and chemokine signalling predisposes to the development of ABPA and is associated with recurring disease.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 259.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 329.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 329.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Latge, J.-P. (1999) Aspergillus fumigatus and Aspergillosis. Clin Microbiol Rev, 12, 310–50.

    CAS  PubMed  Google Scholar 

  2. Latge, J. P. (2001) The pathobiology of Aspergillus fumigatus. Trends Microbiol, 9, 382–89.

    Article  CAS  PubMed  Google Scholar 

  3. Kauffman, H. F. (2003) Immunopathogenesis of allergic bronchopulmonary aspergillosis and airway remodelling. Front Biosci, 8, e190–6.

    Article  CAS  PubMed  Google Scholar 

  4. Iadarola, P., Lungarella, G., Martorana, P. A., Viglio, S., Guglielminetti, M., Korzus, E., Gorrini, M., Cavarra, E., Rossi, A., Travis, J. & Luisetti, M. (1998) Lung injury and degradation of extracellular matrix components by Aspergillus fumigatus serine proteinase. Exp Lung Res, 24, 233–51.

    Article  CAS  PubMed  Google Scholar 

  5. Borger, P., Koeter, G. H., Timmerman, J. A., Vellenga, E., Tomee, J. F. & Kauffman, H. F. (1999) Proteases from Aspergillus fumigatus induce interleukin (IL)-6 and IL-8 production in airway epithelial cell lines by transcriptional mechanisms. J Infect Dis, 180, 1267–74.

    Article  CAS  PubMed  Google Scholar 

  6. Tomee, J. F., Wierenga, A. T., Hiemstra, P. S. & Kauffman, H.K. (1997) Proteases from Aspergillus fumigatus induce release of proinflammatory cytokines and cell detachment in airway epithelial cell lines. J Infect Dis, 176, 300–03.

    Article  CAS  PubMed  Google Scholar 

  7. Kurup,V. P., Banerjee, B. Hemmann,S., Greenberger,P.A., Blaser, K. & Crameri, R. (2000) Selected recombinant Aspergillus fumigatus allergens bind specifically to IgE in ABPA. Clin Exp Allergy, 30, 988–93.

    Article  CAS  PubMed  Google Scholar 

  8. Gautam, P., Sundaram, C. S., Madan, T., Gade, W. N., Shah, A., Sirdeshmukh, R. & Sarma, P. U. (2007) Identification of novel allergens of Aspergillus fumigatus using immunoproteomics approach. Clin Exp Allergy, 37, 1239–49.

    Article  CAS  PubMed  Google Scholar 

  9. Knutsen, A. P., Hutcheson, P. S., Slavin, R. G. & Kurup, V. P. (2004) IgE antibody to Aspergillus fumigatus recombinant allergens in cystic fibrosis patients with allergic bronchopulmonary aspergillosis. Allergy, 59, 198–203.

    Article  CAS  PubMed  Google Scholar 

  10. Patterson, R., Greenberger, P., Radin, R. & Roberts, M. (1982) Allergic bronchopulmonary Aspergillosis: staging as an aid to management. Ann Int Med, 96, 286–91.

    CAS  PubMed  Google Scholar 

  11. Patterson, R., Greenberger, G., Halwig, M., Liotta, J. & Roberts, M. (1986) Allergic bronchopulmonary Aspergillosis. Arch Int Med, 146, 916–18.

    Article  CAS  Google Scholar 

  12. Patterson, R. & Greenberger, P. A. (1995) Allergic Bronchopulmonary Aspergillosis, Providence RI, Oceanside Publications.

    Google Scholar 

  13. Katzenstein, K., Liebow, A. A. & Friedman, P. J. (1975) Bronchocentric granulomatosis. Mucoid impaction and hypersensitivity reactions to fungi. Am Rev Respir Dis, 3, 232–36.

    Google Scholar 

  14. Slavin, R. G., Bedrossian, C. W., Hutcheson, P. S., Pittman, S., Salinas-Madrigal, L., Tsai, C. C. & Gleich, G. J. (1988) A pathologic study of allergic bronchopulmonary aspergillosis. J Allergy Clin Immunol, 81, 718–25.

    Article  CAS  PubMed  Google Scholar 

  15. Walker, C., Bauer, W., Braun, R. K., Menz, G., Braun, P., Schwarz, F., Hansel, T. T. & Villiger, B. (1994) Activated T cells and cytokines in bronchoalveolar lavages from patients with various lung diseases associated with eosinophilia. Am J Respir Crit Care Med, 150, 1038–48.

    CAS  PubMed  Google Scholar 

  16. Wark, P. A. B., Saltos, N., Simpson, J. L., Slater, S., Hensley, M. J. & Gibson, P. G. (2000) Induced sputum eosinophils and neutrophils and bronchiectasis severity in allergic bronchopulmonary aspergillosis. Eur Respir J, 16, 1095–100.

    Article  CAS  PubMed  Google Scholar 

  17. Gibson, P. G., Wark, P. A. B., Simpson, J. L., Meldrum, C., Meldrum, S., Saltos, N. & Boyle, M. (2003) Induced sputum IL-8 gene expression, neutrophil influx and MMP-9 in allergic bronchopulmonary aspergillosis. Eur Respir J, 21, 582–88.

    Article  CAS  PubMed  Google Scholar 

  18. Gibson, R. L., Burns, J. L. & Ramsey, B. W. (2003) Pathophysiology and management of pulmonary infections in cystic fibrosis. Am J Respir Crit Care Med, 168, 918–51.

    Article  PubMed  Google Scholar 

  19. Boucher, R. C. (2007) Evidence for airway surface dehydration as the initiating event in CF airway disease. J Intern Med, 261, 5–16.

    Article  CAS  PubMed  Google Scholar 

  20. Eaton, T. E., Weiner Miller, P., Garrett, J. E. & Cutting, G. R. (2002) Cystic fibrosis transmembrane conductance regulator gene mutations: do they play a role in the aetiology of allergic bronchopulmonary aspergillosis? Clin Exp Allergy, 32, 756–61.

    Article  CAS  PubMed  Google Scholar 

  21. Miller, P. W., Hamosh, A., Macek, M., Greenberger, P. A., Maclean, J., Walden, S. M., Slavin, R. G. & Cutting, G. R. (1996) Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations in allergic bronchopulmonary aspergillosis. Am J Hum Gen, 59, 45–51.

    CAS  Google Scholar 

  22. Marchand, E., Verellin-Dumoulin, C., Mairesse, M., Delanouis, L., Bramncaleonie, P., Rahier, P. & Al, E. (2001) Frequency of cystic fibrosis transmembrane conductance regulator gene mutations and 5t allele in patients with allergic bronchopulmonary aspergillosis. Chest, 119, 762–7.

    Article  CAS  PubMed  Google Scholar 

  23. Zhang, Z., Liu, R., Noordhoek, J. A. & Kauffman, H. F. (2005) Interaction of airway epithelial cells (A549) with spores and mycelium of Aspergillus fumigatus. J Infect, 51, 375–82.

    Article  PubMed  Google Scholar 

  24. Wright, J. R. (2005) Immunoregulatory functions of surfactant proteins. Nat Rev Immunol, 5, 58–68.

    Article  CAS  PubMed  Google Scholar 

  25. Madan, T., Kaur, S., Saxena, S., Singh, M., Kishore, U., Thiel, S., Reid, K. B. & Sarma, P. U. (2005) Role of collectins in innate immunity against aspergillosis. Med Mycol, 43 Suppl 1, S155–63.

    Article  CAS  PubMed  Google Scholar 

  26. Saxena, S., Madan, T., Shah, A., Muralidhar, K. & Sarma, P. (2003) Association of polymorphisms in the collagen region of SP-A2 with increased levels of total IgE antibodies and eosinophilia in patients with allergic bronchopulmonary aspergillosis. J Allergy Clin Immunol, 111, 1001–007.

    Article  CAS  PubMed  Google Scholar 

  27. Roilides, E., Katsifa, H. & Walsh, T. J. (1998) Pulmonary host defences against Aspergillus fumigatus. Res Immunol, 149, 454–65; discussion 523–4.

    Article  CAS  PubMed  Google Scholar 

  28. Chignard, M., Balloy, V., Sallenave, J. M. & Si-Tahar, M. (2007) Role of Toll-like receptors in lung innate defense against invasive aspergillosis. Distinct impact in immunocompetent and immunocompromized hosts. Clin Immunol, 124, 238–43.

    Article  CAS  PubMed  Google Scholar 

  29. Roilides, E., Dimitriadou-Georgiadou, A., Sein, T., Kadiltsoglou, I. & Walsh, T. J. (1998) Tumor necrosis factor alpha enhances antifungal activities of polymorphonuclear and mononuclear phagocytes against Aspergillus fumigatus. Infect Immun, 66, 5999–6003.

    CAS  PubMed  Google Scholar 

  30. Roilides, E., Tsaparidou, S., Kadiltsoglou, I., Sein, T. & Walsh, T. J. (1999) Interleukin-12 enhances antifungal activity of human mononuclear phagocytes against Aspergillus fumigatus: implications for a gamma interferon-independent pathway. Infect Immun, 67, 3047–50.

    CAS  PubMed  Google Scholar 

  31. Shao, C., Qu, J., He, L., Zhang, Y., Wang, J., Wang, Y., Zhou, H. & Liu, X. (2005) Transient overexpression of gamma interferon promotes Aspergillus clearance in invasive pulmonary aspergillosis. Clin Exp Immunol, 142, 233–41.

    Article  CAS  PubMed  Google Scholar 

  32. Bellocchio, S., Moretti, S., Perruccio, K., Fallarino, F., Bozza, S., Montagnoli, C., Mosci, P., Lipford, G. B., Pitzurra, L. & Romani, L. (2004) TLRs govern neutrophil activity in aspergillosis. J Immunol, 173, 7406–15.

    CAS  PubMed  Google Scholar 

  33. Carvalho, A., Pasqualotto, A. C., Pitzurra, L., Romani, L., Denning, D. W. & Rodrigues, F. (2008) Polymorphisms in toll-like receptor genes and susceptibility to pulmonary aspergillosis. J Infect Dis, 197, 618–21.

    Article  CAS  PubMed  Google Scholar 

  34. Lazarus, R., Klimecki, W. T., Raby, B. A., Vercelli, D., Palmer, L. J., Kwiatkowski, D. J., Silverman, E. K., Martinez, F. & Weiss, S. T. (2003) Single-nucleotide polymorphisms in the Toll-like receptor 9 gene (TLR9): frequencies, pairwise linkage disequilibrium, and haplotypes in three U.S. ethnic groups and exploratory case-control disease association studies. Genomics, 81, 85–91.

    Article  CAS  PubMed  Google Scholar 

  35. Borisch, L., Aarons, A., Rumbyrt, J., Cvietusa, P., Negri, J. & Wenzel, S. (1996) Interleukin-10 regulation in normal subjects and patients with asthma. J Allergy Clin Immunol, 97, 1288–96.

    Article  Google Scholar 

  36. Grunig, G., Corry, D. B., Leach, M. W., Seymour, B. W., Kurup, V. P. & Rennick, D. M. (1997) Interleukin-10 is a natural suppressor of cytokine production and inflammation in a murine model of allergic bronchopulmonary aspergillosis. J Exp Med, 185, 1089–99.

    Article  CAS  PubMed  Google Scholar 

  37. Brouard, J., Knauer, N., Boelle, P. Y., Corvol, H., Henrion-Caude, A., Flamant, C., Bremont, F., Delaisi, B., Duhamel, J. F., Marguet, C., Roussey, M., Miesch, M. C., Chadelat, K., Boule, M., Fauroux, B., Ratjen, F., Grasemann, H. & Clement, A. (2005) Influence of interleukin-10 on Aspergillus fumigatus infection in patients with cystic fibrosis. J Infect Dis, 191, 1988–91.

    Article  CAS  PubMed  Google Scholar 

  38. Greenberger, P. A., Smith, L. J., Hsu, C. C., Roberts, M. & Liotta, J. L. (1988) Analysis of bronchoalveolar lavage in allergic bronchopulmonary aspergillosis: divergent responses of antigen specific antibodies and total IgE. J Allergy Clin Immunol, 82, 164–70.

    Article  CAS  PubMed  Google Scholar 

  39. Chauhan, B., Knutsen, A., Hutcheson, P. S., Slavin, R. G. & Bellone, C. J. (1996) T cell subsets, epitope mapping, and HLA-restriction in patients with allergic bronchopulmonary aspergillosis. J Clin Invest, 97, 2324–31.

    Article  CAS  PubMed  Google Scholar 

  40. Chauhan, B., Santiago, L., Kirschmann, D. A., Hauptfeld, V., Knutsen, A. P., Hutcheson, P. S., Woulfe, S. L., Slavin, R. G., Schwartz, H. J. & Bellone, C. J. (1997) The association of HLA-DR alleles and T cell activation with allergic bronchopulmonary aspergillosis. J Immunol, 159, 4072–6.

    CAS  PubMed  Google Scholar 

  41. Koehm, S., Slavin, R. G., Hutcheson, P. S., Trejo, T., David, C. S. & Bellone, C. J. (2007) HLA-DRB1 alleles control allergic bronchopulmonary aspergillosis-like pulmonary responses in humanized transgenic mice. J Allergy Clin Immunol, 120, 570–7.

    Article  CAS  PubMed  Google Scholar 

  42. Knutsen, A. P. (2003) Lymphocytes in allergic bronchopulmonary aspergillosis. Front Biosci, 8, d589–602.

    Article  CAS  PubMed  Google Scholar 

  43. Chauhan, B., Hutcheson, P. S., Slavin, R. G. & Bellone, C. J. (2002) T-cell receptor bias in patients with allergic bronchopulmonary aspergillosis. Hum Immunol, 63, 286–94.

    Article  CAS  PubMed  Google Scholar 

  44. D’ambrosio, D., Iellem, A., Bonecchi, R., Mazzeo, D., Sozzani, S., Mantovani, A. & Sinigaglia, F. (1998) Selective up-regulation of chemokine receptors CCR4 and CCR8 upon activation of polarized human type 2 Th cells. J Immunol, 161, 5111–5.

    PubMed  Google Scholar 

  45. Schuh, J. M., Power, C. A., Proudfoot, A. E., Kunkel, S. L., Lukacs, N. W. & Hogaboam, C. M. (2002) Airway hyperresponsiveness, but not airway remodeling, is attenuated during chronic pulmonary allergic responses to Aspergillus in CCR4–/– mice. Faseb J, 16, 1313–5.

    CAS  PubMed  Google Scholar 

  46. Hartl, D., Latzin, P., Zissel, G., Krane, M., Krauss-Etschmann, S. & Griese, M. (2006) Chemokines indicate allergic bronchopulmonary aspergillosis in patients with cystic fibrosis. Am J Respir Crit Care Med, 173, 1370–76.

    Article  CAS  PubMed  Google Scholar 

  47. Garcia, G., Humbert, M., Capel, F., Rimaniol, A. C., Escourrou, P., Emilie, D. & Godot, V. (2007) Chemokine receptor expression on allergen-specific T cells in asthma and allergic bronchopulmonary aspergillosis. Allergy, 62, 170–77.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Respiratory and Sleep Medicine, Centre for Asthma and Respiratory Disease Hunter Medical Research Institute, John Hunter Hospital, University of Newcastle, NSW 2305, Lookout Rd New Lambton, Australia

    Peter A.B. Wark

  2. Centre for Asthma and Respiratory Disease, Hunter Medical Research Institute, University of Newcastle, New Lambton, NSW, Australia

    Peter Gibson

Authors
  1. Peter A.B. Wark
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Peter Gibson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Peter A.B. Wark .

Editor information

Editors and Affiliations

  1. Porto Alegre, Complexo Hospitalar Santa Casa de, Av. Independencia 155, Porto Alegre, 90035-075, Brazil

    Alessandro Comarú Pasqualotto

Rights and permissions

Reprints and permissions

Copyright information

© 2009 Springer Science+Business Media B.V.

About this chapter

Cite this chapter

Wark, P.A., Gibson, P. (2009). Pathogenesis of ABPA. In: Comarú Pasqualotto, A. (eds) Aspergillosis: From Diagnosis to Prevention. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-2408-4_41

Download citation

Publish with us

Policies and ethics

Search

Navigation