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Experimental paracoccidioidomycosis in the Syrian hamster

Morphology and correlation of lesions with humoral and cell-mediated immunity

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Abstract

Male hamsters (105) received intratesticular injection of suspension of a live yeast phase culture ofParacoccidioides brasiliensis and were sacrificed weekly during 20 weeks. Humoral immunity was studied by the agar-gel immunodiffusion (ID) and indirect immunofluorescence (IF) tests. Cell-mediated immunity was determined by the macrophage migration inhibition test in the presence of phytohemagglutinin (PHA) andParacoccidioides brasiliensis soluble antigen (PbAg). The morphology of the lesions was studied in the inoculation site, lymph nodes, lung, liver, spleen and kidneys.

Disseminated paracoccidioidomycosis was observed in 100% of the animals after the first week. The lesions were initially made up of fungi surrounded by polymorphonuclear neutrophils and macrophages. Up to the 10th week the majority of the lesions appeared as compact confluent ephitelioid granulomas containing rare large fungi, some showing signs of degeneration. At this time, the specific antibody titers and the cellular immune response to PHA and PbAg were highest.

From the 11th week on the granulomas became less compact, edematous with the epithelioid cells loosely arranged. This change was accompanied by an increase in the number of fungi showing reproductive activity and was associated with renal amyloidosis and progressive decline of cellular immune response both to PHA and PbAg. Contrariwise the titers of circulating antibodies were maintained.

In the present model, disseminated paracoccidioidomycosis of the hamster was associated with depression of cellular immunity, change in the pattern of the granuloma, intense fungi proliferation and amyloidosis.

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References

  1. Adams, D. O., 1976. The granulomatous inflammatory response. A review. Am. J. Pathol. 84: 164–192.

    Google Scholar 

  2. Ando, M., Dannenberg Jr., A. M. & Shima, K., 1972. Macrophage accumulation, division, maturation and digestive and microbicidal capacities in tuberculous lesions. II. Rate at with mononuclear cells enter and divide in primary BCG lesions and those of reinfection. J. Immunol. 109: 8–19.

    Google Scholar 

  3. Aoki, N., Pinnamaneni, K. M. & De Groot, L. J., 1979. Studies on suppressor cell function in thyroid diseases. J. Clin. Endocr. Metab. 48: 803–810.

    Google Scholar 

  4. Artz, R. P. & Bullock, W. E., 1979. Immunoregulatory responses in experimental disseminated histoplasmosis: depression of T-cell-dependent and T-effector responses by activation of splenic suppressor cells. Infect. Immun. 23: 893–902.

    Google Scholar 

  5. Attalah, A. M., Smith, A. H., Murrell, K. D., Fleisher, T., Woody, J., Vannier, W. E., Scher, I., Ahmed, A. & Sell, K. W., 1979. Characterization of the immunosuppressive state during Schistosoma mansoni infection. J. Immunol. 122: 1413–1420.

    Google Scholar 

  6. Bennett, J. E., Hasenclever, J. F. & Baum, G. L., 1965. Evaluation of a skin test for cryptococcosis. An. Rev. Resp. Dis. 91: 616.

    Google Scholar 

  7. Bernd, L. A. G., 1981. Receptor solúvel de linfócitos T para eritrócitos de carneiro: detecção por gel-difusão, dosagem por inibição de linfocitotoxicidade e relação estrutural com alpha globulina imunorreguladora (IRA). Doctorate thesis. Escola Paulista de Medicina, São Paulo.

    Google Scholar 

  8. Biberfeld, G., 1973. Macrophage migration inhibition in resonse to experimental mycoplasma pneumoniae infection in the hamster. J. Immunol. 110: 1146–1150.

    Google Scholar 

  9. Brito, T. de & Fava Netto, C., 1963. Disseminated experimental south american blastomycosis of the guinea pig: a pathologic and immunologic study. Path. Microbiol. (Basel) 26: 29–43.

    Google Scholar 

  10. Bullock, W. E., Carlson, E. M. & Gershon, R. K., 1978. The evolution of immunosuppressive cell populations in experimental mycobacterial infection. J. Immunol. 120: 1709–1713.

    Google Scholar 

  11. Chaparas, S. D., Levine, H. B., Scalarone, G. M. & Papagianis, D., 1975. Cellular responses, protective immunity and virulence in experimental coccidioidomycosis. Scient. Publ. Pan Am. Hlth. Orgn. 304: 80–87.

    Google Scholar 

  12. Chensue, S. W. & Boros, D. L., 1979. Modulation of granulomatous hypersensitivity. I. Characterization of T lymphocytes involved in the adaptive suppression of granuloma formation in Schistosoma mansoni infected mice. J. Immunol. 123: 1409–1414.

    Google Scholar 

  13. Chensue, S. W., Boros, D. L. & David, C. S., 1980. Regulation of granulomatous inflammation in murine Schistosomiasis. In vito characterization of T lymphocyte subsets involved in the production and suppression of MIF. J. Exp. Med. 151: 1398–1412.

    Google Scholar 

  14. Chisari, F. V., Castle, K. L., Xavier, C. & Anderson, D. S., 1981. Functional properties of lymphocyte subpopulations in hepatitis infection. I. Suppressor cell control of T lymphocytes responsiveness. J. Immunol. 126: 38–44.

    Google Scholar 

  15. Cohn, Z. A., 1975. Macrophage physiology. Fed. Proc. 34: 1725–1729.

    Google Scholar 

  16. Conti-Diaz, I. A. & Furcolow, M. L., 1972. Susceptibility of hamsters and mice to Paracoccicidioides brasiliensis using different routes of inoculation. Mycopathol. Mycol. Appl. 47: 73–79.

    Google Scholar 

  17. Cooperband, S. R., Badger, A. M., Davis, R. C., Schmid, K. & Mannick, J. A., 1972. The effect of immunoregulatory alpha globulin(IRA) upon lymphocytes in vitro. J. Immunol. 109: 154–163.

    Google Scholar 

  18. Cooperband, S. R., Nimberg, R., Schmid, K. & Mannick, J. A., 1976. Humoral immunosuppressive factors. Transplant. Proc. 8: 225–242.

    Google Scholar 

  19. Costa, E. O. de, Fava Netto C., Rodrigues, S. & Brito, T. de, 1978. Bovine experimental paracoccidioidomycosis. Intradermic test standardization. Sabouraudia 16: 103–113.

    Google Scholar 

  20. Davies, P. & Allison, A. C., 1975. Secretion of macrophage enzymes in relation to the pathogenesis of chronic inflammation. Immunobiology of the macrophage. Edited by D. S. Nelson. New York, Academic Press, Inc., pp. 428–463.

    Google Scholar 

  21. Defaveri, J., Rezkallah-Iwasso, M. T. & Franco, M. F., 1981. Experimental pulmonary paracoccidioidomycosis in mice: morphology and correlation of lesions with humoral and cellular immune response. Mycopathologia (in press).

  22. Domingo, E. O. & Warren, K. S., 1967. The inhibiton of granuloma formation around Schistosoma mansoni eggs. II. Thymectomy. Am. J. Path. 51: 757–767.

    Google Scholar 

  23. Druet, R. L. & Janigan, D. T., 1966. Experimental amyloidosis. Rates of induction, lymphocyte depletion and thymic atrophy. Am. J. Path. 49: 911–923.

    Google Scholar 

  24. Fava Netto, C., 1965. The immunology of south-american blastomycosis. Mycopathol. Mycol. Appl. 26: 349–358.

    Google Scholar 

  25. Fava Netto, C., Ferri, R. G. & Lacaz, C. S., 1959. Proteinograma e algumas ‘provas de fase aguda do soro’ na blastomicose sul-americana. Estudo comparativo com as reações de fixação do complemento e precipitação. Med. Cirurg. Farm. 277: 157–163.

    Google Scholar 

  26. Fava Netto, C., Brito T. de & Lacaz, C. da S., 1961. Experimental south-american blastomycosis of the guinea pig. An immunologic and pathologic study. Path. Microbiol. (Basel) 24: 192–206.

    Google Scholar 

  27. Fava Netto, C., Vegas, V. S., Sciannamea, I. M. & Guarnieri, D. B., 1969. Antigeno polissacarídico do Paracoccidioides brasiliensis. Estudo do tempo de cultivo do P. brasiliensis necessário ao preparo do antígeno. Rev. Inst. Med. Trop. S. Paulo 11: 177–181.

    Google Scholar 

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

    Google Scholar 

  29. Franklin, E. C. & Clerici, E., 1974. Amyloid. In: L. Brent & J. Holborow. Prog. Immunol. II 4: 381–384.

    Google Scholar 

  30. Glenner, G. G., 1980. Amyloid deposits and amyloidosis. New. Engl. J. Med. 302: 1283–1292.

    Google Scholar 

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

    Google Scholar 

  32. Guimarães, F. N., 1951. Infecção do hamster (Cricetus auratus Waterhouse) pelo agente da micose de Lutz(blastomicose sul-americana). Hospital (Rio de J.) 40: 515–520.

    Google Scholar 

  33. Heilman, D. H. & McFarland, W., 1966. Inhibition of tuberculin-induced mitogenesis in cultures of lymphocytes from tuberculous donors. Int. Arch. Allergy 30: 58–66.

    Google Scholar 

  34. Holt, P. G., 1979. Alveolar macrophages. III. Studies on the mechanism of inhibition of T-cell proliferation. Immunology 37: 437–445.

    Google Scholar 

  35. Horwitz, D. A., Garrett, M. A. & Craig, A. H., 1977. Serum effects on mitogenic reactivity in subjects with systemic lupus erythematosus, rheumatoid arthritis and scleroderma. Technical considerations and lack of correlation with anti-lymphocyte antibodies. Clin. Exp. Immunol. 27: 100–110.

    Google Scholar 

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

    Google Scholar 

  37. Informe Técnico da OMS. 1973. Immunidad celular y resistência a las infecciones: informe de un grupo científico de la O.M.S. Org. Mund. Sal. Ser. Inf. Téc. 519: 1–63.

    Google Scholar 

  38. James, S. L. & Colley, D. G., 1975. Eosinophils and immune mechanisms. Production of the lymphokine eosinophil stimulation promoter (ESP) in vitro by isolated intact granulomas. J. Reticuloendothel. Soc. 18: 283–293.

    Google Scholar 

  39. Lacaz, C. da S., 1956. South american blastomycosis. An. Fac. Med. S. Paulo 29: 1–120.

    Google Scholar 

  40. Larsh, H. W., 1975. Pathogenesis of experimental cryptococcosis and histoplasmosis induced by the airbone route. Scient. Publ. Pan Am. Hlth Orgn. 304: 67–71.

    Google Scholar 

  41. Lazo, R. F., 1968. La inmunodifusion en el diagnostico de la blastomicosis sudamericana. Revta Ecuat. Hig. Med. Trop. 25: 253–260.

    Google Scholar 

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

    Google Scholar 

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

    Google Scholar 

  44. Mattingly, J. A., Eardley, D. D. & Gershon, R. K., 1979. Induction of suppressor cells in rat spleen: influence of microbial stimulation. J. Immunol. 122: 787–790.

    Google Scholar 

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

    Google Scholar 

  46. Mós, E. N., Fava Netto, C., Saliba, A. M. & Brito, T. de, 1974. Contribuição ao estudo da paracoccidoidomicose. II. Infecção experimental do cão. Rev. Inst. Med. trop. S. Paulo 16: 232–237.

    Google Scholar 

  47. 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 

  48. Musatti, C. C., Soares, V. A., Santos, L. M. B., Lima, J. J. G. & Mendes, N. F., 1979. Immunosuppressive effect of soluble E-receptors in uremic serum. Clin. Immunol. Immunopathol. 14: 403–410.

    Google Scholar 

  49. Ortiz-Ortiz, L., Contreras, M. F. & Melendro, E. I., 1975. Cell-mediated immune responses in mice infected with Nocardia brasiliensis. Scient. Publ. Pan. Am. Hlth Orgn. 304: 36–41.

    Google Scholar 

  50. Ouchterlony, O., 1949. Antigen-antibody reaction in gels. Acta Pathol. Microbiol. Scand. 26: 507–515.

    Google Scholar 

  51. Parish, C. R., 1972. The relationship between humoral and cell-mediated immunity. Transplant. Rev. 13: 35–66.

    Google Scholar 

  52. Prager, M. D., Gregg, D. E. & Walter, M. C., 1978. Effect of sera of patients with genitourinary tract cancer on transformation of lymphocytes stimulated with anti-thymocyte globulin. Nat. Cancer Inst. 49: 127–130.

    Google Scholar 

  53. Ramos, C., Schadtler-Siwon, I. & Ortiz-Ortiz, R. L., 1979. Suppressor cells present in the spleens of Trypanosoma cruzi infected mice. J. Immunol. 122: 1243–1247.

    Google Scholar 

  54. Rao, V. S., Bennett, J. A., Grodzicki, R. L. & Mítchell, M. S., 1979. Suppressor T cells induced by soluble immune complexes can adaptively transfer inhibition of cytophilic antibody receptors on macrophage. Cell. Immunol. 46: 227–238.

    Google Scholar 

  55. Restrepo, M. A. & Moncada, L. H. F., 1972. Indirect fluorescent-antibody and quantitative agar-gel immunodiffusion tests for the serological diagnosis of paracoccidioidomycosis. Appl. Microbiol. 24: 132–137.

    Google Scholar 

  56. Rosenthal, C. J. & Franklin, E. C., 1977. Amyloidosis and amyloid proteins. Recent Adv. Clin. Immunol. 1: 41–76.

    Google Scholar 

  57. Salfelder, K., Schwarz, J. & Johnson, C. E., 1968. Experimental cutaneous South American blastomycosis in hamster. Arch. Derm. 97: 69–77.

    Google Scholar 

  58. Scheinberg, M. A., Goldstein, A. L. & Cathcart, E. S., 1976. Thymosin restores T cell function and reduces the incidence of amyloid disease in casein-treated mice. J. Immunol. 116: 156–158.

    Google Scholar 

  59. Scheinberg, M. A. & Cathcart, E. S., 1974. Casein induced experimental amyloidosis. III. Response to mitogens, allogenic cells and graft versus host reactions in the murine model. Immunology 27: 953–963.

    Google Scholar 

  60. Segretain, G. & Drouhet, E., 1955. Blastomycoses experimentales du hamster doré. Ann. Inst. Pasteur 89: 593–596.

    Google Scholar 

  61. Spector, W. G. & Heeson, N., 1969. The production of granulomats by antigen-antibody complexes. J. Path. 98: 31–39.

    Google Scholar 

  62. Tanaka, F., Yonemoto, R. H. & Waldman, S. R., 1979. Blocking factors in sera of breast cancer patients. Cancer 43: 838–847.

    Google Scholar 

  63. Teixeira, G. de A., Machado Filho, J. & Miranda, J. L., 1965. Blastomicose sul americana experimental em ratos com considerações relativas à patogenia das lesões. Hospital (Rio de J.) 68: 1081–1096.

    Google Scholar 

  64. Unanue, E. R., 1978. The immune granulomas. In: D. W. Talmage, B. Rose, K. F. Austen, J. W. Vaugham (Eds), Immunological diseases. U.S.A., Little Browns, vol. I, pp. 297–306.

    Google Scholar 

  65. Valdimarsson, J., Higgs, J. M., Wills, R. S., Yamamura, M., Hobbs, J. R. & Holt, P. J. L., 1973. Immune abnormalities associated with chronic mucocutaneous candidiasis. Cell. Immunol. 6: 248–361.

    Google Scholar 

  66. Valentine, F. T., 1974. Soluble factors produced by lymphocytes. Ann N. Y. Acad. Sci. 221: 317–323.

    Google Scholar 

  67. Waldmann, T. A., 1977. Disorders of suppressor cells in the pathogenesis of immunodeficiency, autoimmune and allergic diseases: human disease associated with disorders of an immunological breaking system. Ann. Allergy 39: 79–86.

    Google Scholar 

  68. Ware, J. L., Folds, J. J. & Baseman, J. B., 1979. Serum of rabbits infected with Treponema pallidum (Nichols) inhibits in vitro transformation of normal rabbits lymphocytes. Cell. Immunol. 42: 363–372.

    Google Scholar 

  69. Warren, K. S., Domingo, E. O. & Cowan, R. B. T., 1967. Granuloma formation arround schistosome eggs as a manifestation of delayed hypersensitivity. Am. J. Path. 51: 735–756.

    Google Scholar 

  70. Zeiss, C. Oberkochen. 1969. Integrating and grain-size disks for turret eyepiece and projection screens. Oberkochen, 37 p.

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Peraçoli, M.T.S., Mota, N.G.S. & Montenegro, M.R. Experimental paracoccidioidomycosis in the Syrian hamster. Mycopathologia 79, 7–17 (1982). https://doi.org/10.1007/BF00636175

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