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Experimental pulmonary paracoccidioidomycosis in mice: Morphology and correlation of lesions with humoral and cellular immune response

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Abstract

The present paper describes a murine model for pulmonary paracoccidioidomycosis injecting 6×105 yeast forms ofParacoccidioides brasiliensis (Pb) by the direct intratracheal route. The sequential histopathology of lung and dissemination lesions together with humoral (immunodiffusion test) and cellular immune response (footpad test and macrophage inhibition factor assay — MIF assay) were investigated since the 1st to the 360th day after infection. All infected animal showed pulmonary Pbmycosis up to Day 30; onwards the lesions subsided being found only in one mouse at Day 360. Dissemination lesions were observed in paratracheal and cervical lymph nodes in 9 out of 68 infected animals. Histologically early lesions were rich in polymorphonuclear cells and evolved to a macrophage desquamative pneumonitis at Day 15 and to typical epithelioid granulomata from Day 30 up to Day 360. Specific precipitating antibodies were first detected 15 days after infection, peaked from Day 30 to 60 and were not observed at Day 360. Significant cell-mediated immunity to Pb was noted at Day 15 with the peak reaction at Day 60 and 90.

The intratracheal route represents a highly effective way of infecting mouse with Pb. This experimental pulmonary Pbmycosis is a granulomatous inflammation which courses with specific humoral and cellular immune response. It may be a good tool for further investigation in the pathogenesis and natural history of the disease.

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References

  1. Adams, D. O., 1976. The granulomatous inflammatory response. A review. Am. J. Pathol. 84: 164–191.

    Google Scholar 

  2. Bernardo, I., Hunninghake, G. W., Gadek, J. E., Ferrans, V. J. & Crystal, R. G., 1979. Acute hypersensitivity pneumonities: serial changes in lung lymphocyte subpopulations after exposure to antigen. Am. Rev. Respir. Dis. 120: 985–993.

    Google Scholar 

  3. Brito, T. & Fava Netto, C., 1963. Disseminated experimental South American blastomycosis of the guinea pig. A pathologic and immunologic study. Path. Microbiol. 26: 29–43.

    Google Scholar 

  4. Brito, T., Furtado, J. S., Castro, R. M. & Manini, M., 1973. Intraepithelial parasitism as an infection mechanism in human paracoccidioidomycosis. Virchows Arch. Abt. A Path. Anat. 361: 129–138.

    Google Scholar 

  5. Campbell, C. C., 1972. The pilot wheel: A change in course. Proc. First Panamerican Symposium on Paracoccidioidomycosis. PAHO Scient. Public. N∘254, pp. 306–312.

    Google Scholar 

  6. Carandina, L. & Magaldi, C., 1974. Inquérito sobre blastomicose Sul-Americana pela intradermo-reação em uma comunidade rural do Municipio de Botucatu, SP (Brasil). Revta. Saúde públ. São Paulo 8: 171–179.

    Google Scholar 

  7. Crowle, A. J., 1975. Delayed hypersensitivity in the mouse. Adv. Immunol. 20: 197–264.

    Google Scholar 

  8. David, J. R., Al-Askari, S., Lawrence, H. S. & Thomas, L., 1964. Delayed hypersensitivity ‘in vitro’. I. The specificity of inhibition of cell migration by antigen. J. Immunol. 93: 264–273.

    Google Scholar 

  9. Fava Netto, C., 1955. Estudos quantitativos sobre a fixação do complemento na blastomicose Sul-Americana, com antígenos polissacaridicos. Archos. Cirurg. Clin. exp. 18: 197–254.

    Google Scholar 

  10. Fialho, A., 1956. Patogenia da blastomicose pulmonar. Revta. bras. Tuberc. Doenç. tórax. 24: 97–118.

    Google Scholar 

  11. Franco, M. F., Fava Netto, C. & Chamma, L. G., 1973. Reação de imunofluorescência indireta para o diagnóstico sorológico da blastomicose Sul-Americana. Padronização da reação e comparação dos resultados com a reação de fixação de complemento. Rev. Inst. Med. Trop. S. Paulo 15: 393–398.

    Google Scholar 

  12. Giraldo, R., Restrepo, A., Gutiérrez, F., Robledo, M., Londoño, F., Hernández, H., Sierra, F. & Calle, G., 1976. Pathogenesis of paracoccidíoidomycosis: a model based on the study of 46 patients. Mycopathol. Mycol. Appl. 58: 63–70.

    Google Scholar 

  13. Graybill, J. R. & Taylor, R. L., 1978. Host defense in cryptococcosis. I. An in vivo model for evaluating immune response. Int. Archs. Allergy Appl. Immun. 57: 101–113.

    Google Scholar 

  14. Grimaldi Filho, G., 1979. Ação de agentes imunoestimuladores (BCG e Levamisole) na Leishmaniose cutânea experimental induzida por Leishmania mexicana em camundongos C3H — Aspectos morfológicos e imunológicos. Master thesis. Universidade Federal da Bahia. Brasil.

    Google Scholar 

  15. Iabuki, K. & Montenegro, M. R., 1979. Experimental paracoccidioidomycosis in the syrian hamster: morphology, ultrastructure and correlation of lesions with the presence of specific antigens and serum levels of antibodies. Mycopathologia 67: 131–141.

    Google Scholar 

  16. Iwama de Mattos, M. C. F., 1975. Cell-block preparation for cytodiagnosis of pulmonary paracoccidioidomycosis. Chest 75: 212.

    Google Scholar 

  17. Kaufman, L., 1970. Serology: its value in the diagnosis of coccidioidomycosis, cryptococcosis, and histoplasmosis. Proc. First International Symposium on Mycosis. PAHO Scient. Public. n∘205, pp. 96–100.

    Google Scholar 

  18. Kong, Y. M. & Levine, H. B., 1967. Experimentally induced immunity in the mycosis. Bact. Rev. 31: 35–53.

    Google Scholar 

  19. Kong, Y. M., Savage, D. C. & Kong, L. N. L., 1966. Delayed dermal hypersensitivity in mice to spherule and mycelial extracts of Coccidioides immitis. J. Bact., 91: 876–883.

    Google Scholar 

  20. Kurita, N., 1979. Cell-mediated immune responses in mice infected with Fonsecae pedrosoi. Mycopathologia, 68: 9–15.

    Google Scholar 

  21. Lawrence, R. M., Huston, A. C. & Hoeprich, P. D., 1977. Reproducible method for induction of pulmonary coccidioidomycosis in mice. J. Infec. Dis. 135: 117–119.

    Google Scholar 

  22. Linares, L. I. & Friedman, L., 1972. Experimental paracoccidioidomycosis in mice. Infect. Immun. 5: 681–687.

    Google Scholar 

  23. Lowry, O. H., Rosebrough, N. J., Farr, A. L. & Ranoall, R. J., 1951. Protein measurement with the Folin phenol reagent. J. Biol. Chem. 193: 265–275.

    Google Scholar 

  24. McMurray, D. & Greer, D. L., 1979. Immune responses in bats following intranasal infection with Histoplasma capsulatum. Am. J. Trop. Med. Hyg. 28: 1036–1039.

    Google Scholar 

  25. Mendes, E. & Raphael, A., 1971. Impaired delayed hypersensitivity in patients with South American blastomycosis. J. Allergy 47: 17–22.

    Google Scholar 

  26. Mok, P. W. Y. & Greer, D. L., 1977. Cell-mediated immune responses in patients with paracoccidioidomycosis. Clin. Exp. Immunol. 28: 89–98.

    Google Scholar 

  27. Moscardi, M. & Franco, M. F., 1980. Paracoccidioidomicose experimental do camundongo. I. Aspectos imunológicos da infecção intraperitoneal. Rev. Inst. Med. Trop. S. Paulo 22: 286–293.

    Google Scholar 

  28. Musatti, C. C., Rezkallah, M. T., Mendes, E. & Mendes, N. F., 1976. In vivo and in vitro evaluation of cell-mediated immunity in patients with paracoccidioidomycosis. Cell. Immunol. 24: 365–378.

    Google Scholar 

  29. Peterson, L. B., Braley, J. F., Calvanico, N. J. & Moore, V. L., 1979. An animal model of hypersensitivity pneumonitis in rabbits. Am. Rev. Respir. Dis. 119: 991–999.

    Google Scholar 

  30. Restrepo, A. M., Robledo, M., Giraldo, R., Hernández, H., Sierra, F., Gutiérrez, F., Londoño, F., López, R. & Calle, G., 1976. The gamut of paracoccidioidomycosis. Am. J. Med. 61: 33–42, 1976.

    Google Scholar 

  31. Restrepo, A. M. & Spinosa, G. G., 1976. Paracoccidioidomicosis experimental del raton inducida por via aerógena. Sabouraudia 14: 299–311.

    Google Scholar 

  32. Spencer, H. D. & Cozad, G. C., 1973. Role of delayed hypersensitivity in blastomycosis of mice. Infect. Immun. 7: 329–334.

    Google Scholar 

  33. Spencer, H. E. & Lieblow, A. A., 1977. In: Pathology of the lung, New York, ed. Pergomon Pergomon, v.1 pp. 263–313.

    Google Scholar 

  34. Teixeira, G. A., Machado Filho, J. & Miranda, J. L., 1965. Blastomicose Sul-Americana experimental. Estudo experimental em ratos com considerações relativas à patogenía das lesões. Hospital, Rio de Janeiro 68: 101–116.

    Google Scholar 

  35. Vieira e Silva, C. R., Iwama de Mattos, M. C. F. & Fujimore, M., 1974. Scanning electron microscopy of Paracoccidioides brasiliensis. Study with and without pooled sera from patients with South American blastomycosis. Mycopathol. Mycol. Appl. 54: 235–251.

    Google Scholar 

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Authors and Affiliations

  1. Departamento de Patologia, Faculdade de Medicina de Botucatu, UNESP, 18600, Botucatu, São Paulo, Brasil

    J. Defaveri & M. F. de Franco

  2. Departamento de Microbiologia e Imunologia do Instituto Básico de Biologia Médica e Agrícola, Botucatu, UNESP, 18600, Botucatu, São Paulo, Brasil

    M. T. Rezkallah-Iwasso

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  1. J. Defaveri
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  2. M. T. Rezkallah-Iwasso
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  3. M. F. de Franco
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Defaveri, J., Rezkallah-Iwasso, M.T. & de Franco, M.F. Experimental pulmonary paracoccidioidomycosis in mice: Morphology and correlation of lesions with humoral and cellular immune response. Mycopathologia 77, 3–11 (1982). https://doi.org/10.1007/BF00588649

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