Skip to main content
NCBI home page
Journal of Clinical Microbiology logoLink to Journal of Clinical Microbiology
. 1996 Jun;34(6):1433–1439. doi: 10.1128/jcm.34.6.1433-1439.1996

Murine model of invasive pulmonary aspergillosis following an earlier stage, noninvasive Aspergillus infection.

R Nawada 1, R Amitani 1, E Tanaka 1, A Niimi 1, K Suzuki 1, T Murayama 1, F Kuze 1
PMCID: PMC229038  PMID: 8735094

Abstract

Aspergillus spp. occasionally cause invasive pulmonary aspergillosis following noninvasive infection in patients with underlying bronchopulmonary disorders regardless of their systemic immunological conditions. We developed a murine model of invasive pulmonary aspergillosis following an earlier stage, noninvasive Aspergillus infection. BALB/c mice were inoculated intratracheally with agarose beads containing Aspergillus fumigatus conidia. Two weeks after inoculation, half of the mice were immunosuppressed with cortisone acetate. During a 4-week observation period, the survival rate of infected immunosuppressed mice was significantly lower (P < 0.01) than that of infected nonimmunosuppressed mice. The number of CFU in the lungs gradually decreased in the nonimmunosuppressed mice, whereas a time-related significant increase (P < 0.05) of CFU was demonstrated in the immunosuppressed mice. In the lungs of the nonimmunosuppressed mice, there was marked accumulation of neutrophils, lymphocytes, and macrophages (in this order) around the agarose beads in the bronchi. Aspergillus hyphae were surrounded by the inflammatory cells and did not invade the lung parenchyma. In contrast, in the immunosuppressed mice, Aspergillus hyphae proliferated markedly and invaded the lung parenchyma after immunosuppression. In this model, the two-dimensional extents of the lesions were also evaluated with an image-processing system. Time-related increase of the area of peribronchial necrotic lesions was significant (P < 0.05) after immunosuppression. This model should therefore be useful for investigating the pathophysiology of noninvasive Aspergillus infection and invasive pulmonary aspergillosis and also for clarifying the mechanism of conversion to the invasive disease from the noninvasive stage.

Full Text

The Full Text of this article is available as a PDF (2.5 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aslam P. A., Eastridge C. E., Hughes F. A., Jr Aspergillosis of the lung--an eighteen-year experience. Chest. 1971 Jan;59(1):28–32. doi: 10.1378/chest.59.1.28. [DOI] [PubMed] [Google Scholar]
  2. Binder R. E., Faling L. J., Pugatch R. D., Mahasaen C., Snider G. L. Chronic necrotizing pulmonary aspergillosis: a discrete clinical entity. Medicine (Baltimore) 1982 Mar;61(2):109–124. doi: 10.1097/00005792-198203000-00005. [DOI] [PubMed] [Google Scholar]
  3. Cash H. A., Woods D. E., McCullough B., Johanson W. G., Jr, Bass J. A. A rat model of chronic respiratory infection with Pseudomonas aeruginosa. Am Rev Respir Dis. 1979 Mar;119(3):453–459. doi: 10.1164/arrd.1979.119.3.453. [DOI] [PubMed] [Google Scholar]
  4. Diamond R. D., Krzesicki R., Epstein B., Jao W. Damage to hyphal forms of fungi by human leukocytes in vitro. A possible host defense mechanism in aspergillosis and mucormycosis. Am J Pathol. 1978 May;91(2):313–328. [PMC free article] [PubMed] [Google Scholar]
  5. Dixon D. M., Polak A., Walsh T. J. Fungus dose-dependent primary pulmonary aspergillosis in immunosuppressed mice. Infect Immun. 1989 May;57(5):1452–1456. doi: 10.1128/iai.57.5.1452-1456.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Eisenstein D. J., Biddinger P. W., Rhodes J. C. Experimental murine invasive pulmonary aspergillosis. Am J Clin Pathol. 1990 Apr;93(4):510–515. doi: 10.1093/ajcp/93.4.510. [DOI] [PubMed] [Google Scholar]
  7. Epstein S. M., Verney E., Miale T. D., Sidransky H. Studies on the pathogenesis of experimental pulmonary aspergillosis. Am J Pathol. 1967 Nov;51(5):769–788. [PMC free article] [PubMed] [Google Scholar]
  8. Gefter W. B., Weingrad T. R., Epstein D. M., Ochs R. H., Miller W. T. "Semi-invasive" pulmonary aspergillosis: a new look at the spectrum of aspergillus infections of the lung. Radiology. 1981 Aug;140(2):313–321. doi: 10.1148/radiology.140.2.7255704. [DOI] [PubMed] [Google Scholar]
  9. George P. J., Boffa P. B., Naylor C. P., Higenbottam T. W. Necrotising pulmonary aspergillosis complicating the management of patients with obstructive airways disease. Thorax. 1983 Jun;38(6):478–480. doi: 10.1136/thx.38.6.478. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hector R. F., Yee E., Collins M. S. Use of DBA/2N mice in models of systemic candidiasis and pulmonary and systemic aspergillosis. Infect Immun. 1990 May;58(5):1476–1478. doi: 10.1128/iai.58.5.1476-1478.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kurup V. P., Sheth N. K. Experimental aspergillosis in rabbits. Comp Immunol Microbiol Infect Dis. 1981;4(2):161–174. doi: 10.1016/0147-9571(81)90002-3. [DOI] [PubMed] [Google Scholar]
  12. Meyer R. D., Young L. S., Armstrong D., Yu B. Aspergillosis complicating neoplastic disease. Am J Med. 1973 Jan;54(1):6–15. doi: 10.1016/0002-9343(73)90077-6. [DOI] [PubMed] [Google Scholar]
  13. Niki Y., Bernard E. M., Edwards F. F., Schmitt H. J., Yu B., Armstrong D. Model of recurrent pulmonary aspergillosis in rats. J Clin Microbiol. 1991 Jul;29(7):1317–1322. doi: 10.1128/jcm.29.7.1317-1322.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Palmer L. B., Greenberg H. E., Schiff M. J. Corticosteroid treatment as a risk factor for invasive aspergillosis in patients with lung disease. Thorax. 1991 Jan;46(1):15–20. doi: 10.1136/thx.46.1.15. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Rafferty P., Biggs B. A., Crompton G. K., Grant I. W. What happens to patients with pulmonary aspergilloma? Analysis of 23 cases. Thorax. 1983 Aug;38(8):579–583. doi: 10.1136/thx.38.8.579. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Rosenberg R. S., Creviston S. A., Schonfeld A. J. Invasive aspergillosis complicating resection of a pulmonary aspergilloma in a nonimmunocompromised host. Am Rev Respir Dis. 1982 Dec;126(6):1113–1115. doi: 10.1164/arrd.1982.126.6.1113. [DOI] [PubMed] [Google Scholar]
  17. Spreadbury C. L., Krausz T., Pervez S., Cohen J. Invasive aspergillosis: clinical and pathological features of a new animal model. J Med Vet Mycol. 1989;27(1):5–15. doi: 10.1080/02681218980000021. [DOI] [PubMed] [Google Scholar]
  18. Tanaka E., Yuba Y., Sato A., Kuze F. Effects of the beige mutation on respiratory tract infection with Pseudomonas aeruginosa in mice. Exp Lung Res. 1994 Jul-Aug;20(4):351–366. doi: 10.3109/01902149409064392. [DOI] [PubMed] [Google Scholar]
  19. Thommi G., Bell G., Liu J., Nugent K. Spectrum of invasive pulmonary aspergillosis in immunocompetent patients with chronic obstructive pulmonary disease. South Med J. 1991 Jul;84(7):828–831. doi: 10.1097/00007611-199107000-00004. [DOI] [PubMed] [Google Scholar]
  20. Turner K. J., Hackshaw R., Papadimitriou J., Perrott J. The pathogenesis of experimental pulmonary aspergillosis in normal and cortisone-treated rats. J Pathol. 1976 Feb;118(2):65–73. doi: 10.1002/path.1711180202. [DOI] [PubMed] [Google Scholar]
  21. Varkey B., Rose H. D. Pulmonary aspergilloma. A rational approach to treatment. Am J Med. 1976 Nov;61(5):626–631. doi: 10.1016/0002-9343(76)90140-6. [DOI] [PubMed] [Google Scholar]
  22. Young R. C., Bennett J. E., Vogel C. L., Carbone P. P., DeVita V. T. Aspergillosis. The spectrum of the disease in 98 patients. Medicine (Baltimore) 1970 Mar;49(2):147–173. doi: 10.1097/00005792-197003000-00002. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Microbiology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES