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Pathogenesis of Chronic Cavitary Pulmonary Aspergillosis: The Importance of the Host Immune System

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Aspergillosis: From Diagnosis to Prevention

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Abstract

Aspergillus species cause a wide spectrum of illnesses in humans, including severe invasive infection in those with immunocompromised states, allergy in atopic patients and indolent progressive infection in those without major immunodeficiency but prior pulmonary insults. This spectrum of disease offers a special opportunity to understand the relationship of the host and pathogen. Chronic cavitary pulmonary aspergillosis (CCPA) is an unusual manifestation of aspergillosis that usually affects middle-aged persons who are mildly or not immunosuppressed. Subtle immune defects in innate immunity (mannose binding protein polymorphisms and more recently in surfactant) have been previously identified in these patients, suggesting that many of the differing manifestations of these conditions might be genetically determined. The role of functional polymorphisms in certain candidate cytokine genes – derived from pathways of Th1 and Th2 immune response that are critical for effective antifungal activity – that could contribute to the risk of developing CCPA has only recently begun to be elucidated. Host immune status and the presence of underlying lung disease are important in determining the type of pulmonary involvement. These novel findings of non-cellular, immunogenetic, qualitative defects in patients with CCPA could explain the devastating consequences of the disease in otherwise healthy individuals without any obvious immune defect.

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References

  1. Hohl, T. M. & Feldmesser, M. (2007) Aspergillus fumigatus: principles of pathogenesis and host defense. Eukaryot Cell, 6, 1953–63.

    Article  CAS  PubMed  Google Scholar 

  2. Binder, R. E., Faling, L. J., Pugatch, R. D., Mahasaen, C. & Snider, G. L. (1982) Chronic necrotizing pulmonary aspergillosis: a discrete clinical entity. Medicine (Baltimore), 61, 109–24.

    Article  CAS  Google Scholar 

  3. Gefter, W. B., Weingrad, T. R., Epstein, D. M., Ochs, R. H. & Miller, W. T. (1981) “Semi-invasive” pulmonary aspergillosis: a new look at the spectrum of aspergillus infections of the lung. Radiology, 140, 313–21.

    CAS  PubMed  Google Scholar 

  4. Denning, D. W., Riniotis, K., Dobrashian, R. & Sambatakou, H. (2003) Chronic cavitary and fibrosing pulmonary and pleural aspergillosis: case series, proposed nomenclature change, and review. Clin Infect Dis, 37 Suppl 3, S265–80.

    Article  PubMed  Google Scholar 

  5. Rhodes, J. C. (1993) Aspergillosis. In: Murphy, J. W., Friedman, H. & Bendinelli, M. (Eds.). Fungal infections and immune responses. Plenum Press, New York, USA.

    Google Scholar 

  6. Waldorf, A. R., Levitz, S. M. & Diamond, R. D. (1984) In vivo bronchoalveolar macrophage defense against Rhizopus oryzae and Aspergillus fumigatus. J Infect Dis, 150, 752–60.

    CAS  PubMed  Google Scholar 

  7. Cenci, E., Mencacci, A., Fe D’ostiani, C., Del Sero, G., Mosci, P., Montagnoli, C., Bacci, A. & Romani, L. (1998) Cytokine- and T helper-dependent lung mucosal immunity in mice with invasive pulmonary aspergillosis. J Infect Dis, 178, 1750–60.

    Article  CAS  PubMed  Google Scholar 

  8. De Repentigny, L., Petitbois, S., Boushira, M., Michaliszyn, E., Senechal, S., Gendron, N. & Montplaisir, S. (1993) Acquired immunity in experimental murine aspergillosis is mediated by macrophages. Infect Immun, 61, 3791–802.

    PubMed  Google Scholar 

  9. Duong, M., Ouellet, N., Simard, M., Bergeron, Y., Olivier, M. & Bergeron, M. G. (1998) Kinetic study of host defense and inflammatory response to Aspergillus fumigatus in steroid-induced immunosuppressed mice. J Infect Dis, 178, 1472–82.

    Article  CAS  PubMed  Google Scholar 

  10. Madan, T., Kishore, U., Singh, M., Strong, P., Hussain, E. M., Reid, K. B. & Sarma, P. U. (2001) Protective role of lung surfactant protein D in a murine model of invasive pulmonary aspergillosis. Infect Immun, 69, 2728–31.

    Article  CAS  PubMed  Google Scholar 

  11. Allen, M. J., Harbeck, R., Smith, B., Voelker, D. R. & Mason, R. J. (1999) Binding of rat and human surfactant proteins A and D to Aspergillus fumigatus conidia. Infect Immun, 67, 4563–9.

    CAS  PubMed  Google Scholar 

  12. Levitz, S. M., Selsted, M. E., Ganz, T., Lehrer, R. I. & Diamond, R. D. (1986) In vitro killing of spores and hyphae of Aspergillus fumigatus and Rhizopus oryzae by rabbit neutrophil cationic peptides and bronchoalveolar macrophages. J Infect Dis, 154, 483–9.

    CAS  PubMed  Google Scholar 

  13. Roilides, E., Blake, C., Holmes, A., Pizzo, P. A. & Walsh, T. J. (1996) Granulocyte-macrophage colony-stimulating factor and interferon-gamma prevent dexamethasone-induced immunosuppression of antifungal monocyte activity against Aspergillus fumigatus hyphae. J Med Vet Mycol, 34, 63–9.

    Article  CAS  PubMed  Google Scholar 

  14. Vaid, M., Kaur, S., Sambatakou, H., Madan, T., Denning, D. W. & Sarma, P. U. (2007) Distinct alleles of mannose-binding lectin (MBL) and surfactant proteins A (SP-A) in patients with chronic cavitary pulmonary aspergillosis and allergic bronchopulmonary aspergillosis. Clin Chem Lab Med, 45, 183–6.

    Article  CAS  PubMed  Google Scholar 

  15. Crosdale, D. J., Poulton, K. V., Ollier, W. E., Thomson, W. & Denning, D. W. (2001) Mannose-binding lectin gene polymorphisms as a susceptibility factor for chronic necrotizing pulmonary aspergillosis. J Infect Dis, 184, 653–6.

    Article  CAS  PubMed  Google Scholar 

  16. Kaur, S., Gupta, V. K., Shah, A., Thiel, S., Sarma, P. U. & Madan, T. (2006) Elevated levels of mannan-binding lectin [corrected] (MBL) and eosinophilia in patients of bronchial asthma with allergic rhinitis and allergic bronchopulmonary aspergillosis associate with a novel intronic polymorphism in MBL. Clin Exp Immunol, 143, 414–9.

    Article  CAS  PubMed  Google Scholar 

  17. Floros, J. & Hoover, R. R. (1998) Genetic of the hydrophilic surfactant protein A and D. Biochim Biophys Acta, 19, 321–22.

    Google Scholar 

  18. Kuroki, Y., Takahashi, H., Chiba, H. & Akino, T. (1998) Surfactant proteins A and D: disease markers. Biochim Biophys Acta, 1408, 334–45.

    CAS  PubMed  Google Scholar 

  19. Mildenberger, E., Demello, D. E., Lin, Z., Kossel, H., Hoehn, T. & Versmold, H. T. (2001) Focal congenital alveolar proteinosis associated with abnormal surfactant protein B messenger RNA. Chest, 119, 645–7.

    Article  CAS  PubMed  Google Scholar 

  20. Tredano, M., Cneude, F., Denamur, E., Truffert, P., Capron, F., Manouvrier, S., Feldmann, D., Couderc, R., Elion, J. & Lacaze-Masmonteil, T. (2000) [Constitutional deficiency of pulmonary surfactant protein B: clinical presentation, histologic and molecular diagnosis]. Arch Pediatr, 7, 641–4.

    Article  CAS  PubMed  Google Scholar 

  21. Garlanda, C., Hirsch, E., Bozza, S., Salustri, A., De Acetis, M., Nota, R., Maccagno, A., Riva, F., Bottazzi, B., Peri, G., Doni, A., Vago, L., Botto, M., De Santis, R., Carminati, P., Siracusa, G., Altruda, F., Vecchi, A., Romani, L. & Mantovani, A. (2002) Non-redundant role of the long pentraxin PTX3 in anti-fungal innate immune response. Nature, 420, 182–6.

    Article  CAS  PubMed  Google Scholar 

  22. Gaziano, R., Bozza, S., Bellocchio, S., Perruccio, K., Montagnoli, C., Pitzurra, L., Salvatori, G., De Santis, R., Carminati, P., Mantovani, A. & Romani, L. (2004) Anti-Aspergillus fumigatus efficacy of pentraxin 3 alone and in combination with antifungals. Antimicrob Agents Chemother, 48, 4414–21.

    Article  CAS  PubMed  Google Scholar 

  23. James, D. G. (1991) James DG. What makes granulomas tick? Thorax, 46, 734–6.

    Article  CAS  PubMed  Google Scholar 

  24. Roman, J., Jeon, Y. J., Gal, A. & Perez, R. L. (1995) Distribution of extracellular matrices, matrix receptors, and transforming growth factor-beta 1 in human and experimental lung granulomatous inflammation. Am J Med Sci, 309, 124–33.

    Article  CAS  PubMed  Google Scholar 

  25. Cenci, E., Perito, S., Enssle, K. H., Mosci, P., Latge, J. P., Romani, L. & Bistoni, F. (1997) Th1 and Th2 cytokines in mice with invasive aspergillosis. Infect Immun, 65, 564–70.

    CAS  PubMed  Google Scholar 

  26. Cenci, E., Mencacci, A., Bacci, A., Bistoni, F., Kurup, V. P. & Romani, L. (2000) T cell vaccination in mice with invasive pulmonary aspergillosis. J Immunol, 165, 381–8.

    CAS  PubMed  Google Scholar 

  27. Cenci, E., Mencacci, A., Del Sero, G., Bacci, A., Montagnoli, C., D’ostiani, C. F., Mosci, P., Bachmann, M., Bistoni, F., Kopf, M. & Romani, L. (1999) Interleukin-4 causes susceptibility to invasive pulmonary aspergillosis through suppression of protective type I responses. J Infect Dis, 180, 1957–68.

    Article  CAS  PubMed  Google Scholar 

  28. Mehrad, B., Moore, T. A. & Standiford, T. J. (2000) Macrophage inflammatory protein-1 alpha is a critical mediator of host defense against invasive pulmonary aspergillosis in neutropenic hosts. J Immunol, 165, 962–8.

    CAS  PubMed  Google Scholar 

  29. Schelenz, S., Smith, D. A. & Bancroft, G. J. (1999) Cytokine and chemokine responses following pulmonary challenge with Aspergillus fumigatus: obligatory role of TNF-alpha and GM-CSF in neutrophil recruitment. Med Mycol, 37, 183–94.

    Article  CAS  PubMed  Google Scholar 

  30. Mehrad, B., Strieter, R. M., Moore, T. A., Tsai, W. C., Lira, S. A. & Standiford, T. J. (1999) CXC chemokine receptor-2 ligands are necessary components of neutrophil-mediated host defense in invasive pulmonary aspergillosis. J Immunol, 163, 6086–94.

    CAS  PubMed  Google Scholar 

  31. Montagnoli, C., Fallarino, F., Gaziano, R., Bozza, S., Bellocchio, S., Zelante, T., Kurup, W. P., Pitzurra, L., Puccetti, P. & Romani, L. (2006) Immunity and tolerance to Aspergillus involve functionally distinct regulatory T cells and tryptophan catabolism. J Immunol, 176, 1712–23.

    CAS  PubMed  Google Scholar 

  32. Sambatakou, H., Pravica, V., Hutchinson, I. V. & Denning, D. W. (2006) Cytokine profiling of pulmonary aspergillosis. Int J Immunogenet, 33, 297–302.

    Article  CAS  PubMed  Google Scholar 

  33. Clemons, K. V., Grunig, G., Sobel, R. A., Mirels, L. F., Rennick, D. & Stevens, D. A. 1998 Role of IL-10 in invasive aspergillosis: Increased resistance of IL-10 gene knockout mice to lethal systemic aspergillosis. in IDSA 36th Annual Meeting.

    Google Scholar 

  34. O’garra, A. & Vieira, P. (2007) T(H)1 cells control themselves by producing interleukin-10. Nat Rev Immunol, 7, 425–8.

    Article  PubMed  Google Scholar 

  35. Zelante, T., De Luca, A., Bonifazi, P., Montagnoli, C., Bozza, S., Moretti, S., Belladonna, M. L., Vacca, C., Conte, C., Mosci, P., Bistoni, F., Puccetti, P., Kastelein, R. A., Kopf, M. & Romani, L. (2007) IL-23 and the Th17 pathway promote inflammation and impair antifungal immune resistance. Eur J Immunol, 37, 2695–706.

    Article  CAS  PubMed  Google Scholar 

  36. Wang, J. E., Warris, A., Ellingsen, E. A., Jorgensen, P. F., Flo, T. H., Espevik, T., Solberg, R., Verweij, P. E. & Aasen, A. O. (2001) Involvement of CD14 and toll-like receptors in activation of human monocytes by Aspergillus fumigatus hyphae. Infect Immun, 69, 2402–06.

    Article  CAS  PubMed  Google Scholar 

  37. Mambula, S. S., Sau, K., Henneke, P., Golenbock, D. T. & Levitz, S. M. (2002) Toll-like receptor (TLR) signaling in response to Aspergillus fumigatus. J Biol Chem, 277, 393202–6.

    Article  Google Scholar 

  38. Meier, A., Kirschning, C. J., Nikolaus, T., Wagner, H., Heesemann, J. & Ebel, F. (2003) Toll-like receptor (TLR) 2 and TLR4 are essential for Aspergillus-induced activation of murine macrophages. Cell Microbiol, 5, 561–70.

    Article  CAS  PubMed  Google Scholar 

  39. Netea, M. G., Warris, A., Van Der Meer, J. W., Fenton, M. J., Verver-Janssen, T. J., Jacobs, L. E., Andresen, T., Verweij, P. E. & Kullberg, B. J. (2003) Aspergillus fumigatus evades immune recognition during germination through loss of toll-like receptor-4-mediated signal transduction. J Infect Dis, 188, 320–26.

    Article  CAS  PubMed  Google Scholar 

  40. 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 

  41. Kesh, S., Mensah, N. Y., Peterlongo, P., Jaffe, D., Hsu, K., M, V. D. B., O’reilly, R., Pamer, E., Satagopan, J. & Papanicolaou, G. A. (2005) TLR1 and TLR6 polymorphisms are associated with susceptibility to invasive aspergillosis after allogeneic stem cell transplantation. Ann N Y Acad Sci, 1062, 95–103.

    Google Scholar 

  42. 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 

  43. Nierman, W. C., Pain, A., Anderson, M. J., Wortman, J. R., Kim, H. S., Arroyo, J., Berriman, M., Abe, K., Archer, D. B., Bermejo, C., Bennett, J., Bowyer, P., Chen, D., Collins, M., Coulsen, R., Davies, R., Dyer, P. S., Farman, M., Fedorova, N., Feldblyum, T. V., Fischer, R., Fosker, N., Fraser, A., Garcia, J. L., Garcia, M. J., Goble, A., Goldman, G. H., Gomi, K., Griffith-Jones, S., Gwilliam, R., Haas, B., Haas, H., Harris, D., Horiuchi, H., Huang, J., Humphray, S., Jimenez, J., Keller, N., Khouri, H., Kitamoto, K., Kobayashi, T., Konzack, S., Kulkarni, R., Kumagai, T., Lafon, A., Latge, J. P., Li, W., Lord, A., Lu, C., Majoros, W. H., May, G. S., Miller, B. L., Mohamoud, Y., Molina, M., Monod, M., Mouyna, I., Mulligan, S., Murphy, L., O’neil, S., Paulsen, I., Penalva, M. A., Pertea, M., Price, C., Pritchard, B. L., Quail, M. A., Rabbinowitsch, E., Rawlins, N., Rajandream, M. A., Reichard, U., Renauld, H., Robson, G. D., Rodriguez De Cordoba, S., Rodriguez-Pena, J. M., Ronning, C. M., Rutter, S., Salzberg, S. L., Sanchez, M., Sanchez-Ferrero, J. C., Saunders, D., Seeger, K., Squares, R., Squares, S., Takeuchi, M., Tekaia, F., Turner, G., Vazquez De Aldana, C. R., Weidman, J., White, O., Woodward, J., Yu, J. H., Fraser, C., Galagan, J. E., Asai, K., Machida, M., Hall, N., Barrell, B. & Denning, D. W. (2005) Genomic sequence of the pathogenic and allergenic filamentous fungus Aspergillus fumigatus. Nature, 438, 1151–56.

    Article  CAS  PubMed  Google Scholar 

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  1. Second Department of Internal Medicine and Infectious Diseases Unit, Hippokration General Hospital, The University of Athens, 11527, Athens, Greece

    Helen Sambatakou

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  1. Helen Sambatakou
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Correspondence to Helen Sambatakou .

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

    Alessandro Comarú Pasqualotto

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Sambatakou, H. (2009). Pathogenesis of Chronic Cavitary Pulmonary Aspergillosis: The Importance of the Host Immune System. In: Comarú Pasqualotto, A. (eds) Aspergillosis: From Diagnosis to Prevention. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-2408-4_36

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