Experimental coccidioidomycosis in the immunosuppressed rat

Remesar, Mirta C.; Blejer, Jorgelina L.; Negroni, Ricardo; Nejamkis, Marta R.

doi:10.1590/S0036-46651992000400006

Abstracts

C. immitis inoculated rats are known to develop infection restricted to lung whereas cyclophosphamide (CY) treatment leads to widespread dissemination with considerable mortality. In this study, an attempt was made to elucidate the mechanisms involved in such behaviour. With this aim, spleen cells were transferred from infected CY-treated to infected untreated rats, achieving significant specific inhibition in footpad swelling to coccidioidin in recipients, attributable to a suppressor T cell subpopulation induced by greater fungal antigen concentration arising from widespread C. immitis dissemination in immunosuppressed animals. NK activity proved similar regardless of CY treatment. Lastly, chronically infected rats presented increased colony forming units count after several weekly doses of CY, as happens in immunosuppressed patients harbouring a previous infection.

Rat; Coccidioidomycosis; Cyclophosphamide; Immunosuppression; T suppressor cells; Reactivation

Ratos adultos inoculados com C. immitis desenvolveram infecção circunscrita ao pulmão sem apresentar mortalidade; no entanto, ao serem imunossuprimidos com CY apresentaram disseminação fúngica em vários órgãos, ausência de granulomas e depressão na resposta celular à coccidioidina junto com uma mortalidade de 50%. Tentou-se determinar os mecanismos envolvidos neste comportamento. Para isso foram medidas as atividades dos linfócitos supressores e células NK. Ao serem transferidos esplenócitos de animais infectados e tratados com CY a ratos somente infectados conseguiu-se significativa inibição específica da resposta à coccidioidina. Este efeito seria devido a uma subpopulação de linfócitos T supressores induzida por maior concentração de antígeno nos animais imunossuprimidos. A atividade NK foi semelhante nos ratos infectados independentemente do tratamento com CY. Por outro lado, tentou-se a reativação da infecção crônica com C. immitis. Os animais infectados apresentaram maior quantidade de unidades formadoras de colônias nos pulmões depois de várias doses semanais de CY, assim como ocorre em pacientes que apresentam deficiências a nível imunológico.

ORIGINAL ARTICLES

Experimental coccidioidomycosis in the immunosuppressed rat

Coccidioidomicose experimental em ratos imunossuprimidos

Mirta C. Remesar; Jorgelina L. Blejer; Ricardo Negroni; Marta R. Nejamkis

From the Department of Microbiology, Faculty of Medicine, Buenos Aires University, Argentina

^{Address for correspondence} Address for correspondence: Dr. M.R. Nejamkis Departamento de Microbiología, Facultad de Medicina Paraguay 2155, Piso 12 1121 Buenos Aires, Argentina

SUMMARY

C. immitis inoculated rats are known to develop infection restricted to lung whereas cyclophosphamide (CY) treatment leads to widespread dissemination with considerable mortality. In this study, an attempt was made to elucidate the mechanisms involved in such behaviour. With this aim, spleen cells were transferred from infected CY-treated to infected untreated rats, achieving significant specific inhibition in footpad swelling to coccidioidin in recipients, attributable to a suppressor T cell subpopulation induced by greater fungal antigen concentration arising from widespread C. immitis dissemination in immunosuppressed animals. NK activity proved similar regardless of CY treatment. Lastly, chronically infected rats presented increased colony forming units count after several weekly doses of CY, as happens in immunosuppressed patients harbouring a previous infection.

Key words: Rat; Coccidioidomycosis; Cyclophosphamide; Immunosuppression; T suppressor cells; Reactivation.

RESUMO

Ratos adultos inoculados com C. immitis desenvolveram infecção circunscrita ao pulmão sem apresentar mortalidade; no entanto, ao serem imunossuprimidos com CY apresentaram disseminação fúngica em vários órgãos, ausência de granulomas e depressão na resposta celular à coccidioidina junto com uma mortalidade de 50%. Tentou-se determinar os mecanismos envolvidos neste comportamento. Para isso foram medidas as atividades dos linfócitos supressores e células NK. Ao serem transferidos esplenócitos de animais infectados e tratados com CY a ratos somente infectados conseguiu-se significativa inibição específica da resposta à coccidioidina. Este efeito seria devido a uma subpopulação de linfócitos T supressores induzida por maior concentração de antígeno nos animais imunossuprimidos. A atividade NK foi semelhante nos ratos infectados independentemente do tratamento com CY. Por outro lado, tentou-se a reativação da infecção crônica com C. immitis. Os animais infectados apresentaram maior quantidade de unidades formadoras de colônias nos pulmões depois de várias doses semanais de CY, assim como ocorre em pacientes que apresentam deficiências a nível imunológico.

Full text available only in PDF format.

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ACKNOWLEDGEMENT

This work was supported by Grants from CONICET and from the Buenos Aires University.

Recebido para publicação em 26/09/1991

Aceito para publicação em 03/07/1992

1. BEAMAN, L.; PAPPAGIANIS, D. & BENJAMIM, E. - Mechanisms of resistance to infection with Coccidioides immitis in mice. Infect. Immun., 23: 681-685, 1979.
2. CATANZARO, A.; SPITLER, L. & MOSER, K. - Cellular immune response in coccidioidomycosis. Cell. Immunol., 15: 360-371, 1975.
3. CLEMONS, K.; LEATHERS, C. & LEE, K. - Systemic Coccidioides immitis infection in nude and beige mice. Infect. Immun., 47: 814-821, 1985.
4. COX, R. & VIVAS, J. - Spectrum of in vivo and in vitro cell-mediated immune responses in coccidioidomycosis. Cell Immunol., 31: 130-141, 1977.
5. COX, R. & KENNELL, W. - Suppression of T-lymphocyte response by Coccidioides immitis antigen. Infect. Immun., 56: 1424-1429, 1988.
6. CHAPARAS, D.; LEVINE, H.; SCALARONE, G. & PAPPAGIANIS, D. - Cellular response, protective immunity and virulence in experimental coccidioidomycosis. In: INTERNATIONAL CONFERENCE ON THE MYCOSES, 3. Washington, Pan American Health Organization, 1975. Procedings. p. 72-79.
7. DRUTZ, D. & HUPPERT, M. - Coccidioidomycosis: factors affecting the host-parasite interaction. J. infect. Dis., 147: 372-390, 1983.
8. ELIAS COSTA, M.; NEGRONI, R. & GIMENO, S. - Estudo biológico de un exoantígeno del Coccidioides immitis. Rev. argent. Micol., 9: 9-11, 1985.
9. HIDORE, M. & MURPHY, J. - Natural cellular resistance of beige mice against Cryptococcus neoformans. J. Immunol., 137: 3624-3631, 1986.
10. LIPSCOMB, M.; ALVARELLOS, T.; TOEWS, G.; TOMPKIS, R.; EVANS, Z.; KOO, G. & KUMAR, V. - Role of natural killer cells in resistance to Cryptococcus neoformans infection in mice. Amer. J. Path., 128: 354-361, 1987.
11. MURPHY, J. & MC DANIEL, D. - In vitro reactivity of natural killer (NK) cells against Cryptococcus neoformans. J. Immunol., 128: 1577-1583, 1982.
12. NEGRONI, R.; FINQUELIEVICH, J. & ELIAS COSTA, M. - Estudio de la coccidioidomicosis experimental en ratas Wistar. Rev. argent. Micol., 8: 7-11, 1985.
13. NICKERSON, D.; HAVENS, R. & BULLECK, W. - Immunoregulation in disseminated histoplasmosis: characterization of splenic suppressor cell populations. Cell. Immunol., 60: 287-297, 1981.
14. OPELZ, G. & SCHEER, M. - Cutaneous sensitivity and in vitro responsiveness of lymphocytes in patients with disseminated coccidioidomycosis, J. infect. Dis., 15: 360-371, 1975.
15. PAPPAGIANIS, D. - Coccidioidomicosis. In: BALOWS, A.; HANSLER, W.; OHASHI, M. & TURANO, A., ed. - Laboratory diagnosis of infectious diseases. Principles and Practice. New York, Springer Verlag, 1988. v.1, p. 677-686.
16. PETKUS, A. & BAUM, L. - Natural killer cell inhibition of young spherules and endospores of Coccidioides immitis. J. Immunol., 139: 3107-3111, 1987.
17. REMESAR, M.; BLEJER, J.; NEGRONI, R. & NEJAMKIS, M. - Cyclophosphamide effect on coccidioidomycosis in the rat. Rev. Inst. Med. trop. S. Paulo, 31: 423-429, 1989.
18. STEVENS, D. - Clinical manifestations and management of coccidioidomycosis in the compromised patient. In: WARNOCK, D. & RICHARDSON, M., ed. - Fungal infections in the compromised patient. New York, J. Willey & Sons, 1982. p. 199-205.

Address for correspondence:

Dr. M.R. Nejamkis

Departamento de Microbiología, Facultad de Medicina

Paraguay 2155, Piso 12

1121 Buenos Aires, Argentina

Publication Dates

Publication in this collection
12 Sept 2006
Date of issue
Aug 1992

History

Accepted
03 July 1992
Received
26 Sept 1991

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

[1] 1. BEAMAN, L.; PAPPAGIANIS, D. & BENJAMIM, E. - Mechanisms of resistance to infection with Coccidioides immitis in mice. Infect. Immun., 23: 681-685, 1979.

[2] 2. CATANZARO, A.; SPITLER, L. & MOSER, K. - Cellular immune response in coccidioidomycosis. Cell. Immunol., 15: 360-371, 1975.

[3] 3. CLEMONS, K.; LEATHERS, C. & LEE, K. - Systemic Coccidioides immitis infection in nude and beige mice. Infect. Immun., 47: 814-821, 1985.

[4] 4. COX, R. & VIVAS, J. - Spectrum of in vivo and in vitro cell-mediated immune responses in coccidioidomycosis. Cell Immunol., 31: 130-141, 1977.

[5] 5. COX, R. & KENNELL, W. - Suppression of T-lymphocyte response by Coccidioides immitis antigen. Infect. Immun., 56: 1424-1429, 1988.

[6] 6. CHAPARAS, D.; LEVINE, H.; SCALARONE, G. & PAPPAGIANIS, D. - Cellular response, protective immunity and virulence in experimental coccidioidomycosis. In: INTERNATIONAL CONFERENCE ON THE MYCOSES, 3. Washington, Pan American Health Organization, 1975. Procedings. p. 72-79.

[7] 7. DRUTZ, D. & HUPPERT, M. - Coccidioidomycosis: factors affecting the host-parasite interaction. J. infect. Dis., 147: 372-390, 1983.

[8] 8. ELIAS COSTA, M.; NEGRONI, R. & GIMENO, S. - Estudo biológico de un exoantígeno del Coccidioides immitis. Rev. argent. Micol., 9: 9-11, 1985.

[9] 9. HIDORE, M. & MURPHY, J. - Natural cellular resistance of beige mice against Cryptococcus neoformans. J. Immunol., 137: 3624-3631, 1986.

[10] 10. LIPSCOMB, M.; ALVARELLOS, T.; TOEWS, G.; TOMPKIS, R.; EVANS, Z.; KOO, G. & KUMAR, V. - Role of natural killer cells in resistance to Cryptococcus neoformans infection in mice. Amer. J. Path., 128: 354-361, 1987.

[11] 11. MURPHY, J. & MC DANIEL, D. - In vitro reactivity of natural killer (NK) cells against Cryptococcus neoformans. J. Immunol., 128: 1577-1583, 1982.

[12] 12. NEGRONI, R.; FINQUELIEVICH, J. & ELIAS COSTA, M. - Estudio de la coccidioidomicosis experimental en ratas Wistar. Rev. argent. Micol., 8: 7-11, 1985.

[13] 13. NICKERSON, D.; HAVENS, R. & BULLECK, W. - Immunoregulation in disseminated histoplasmosis: characterization of splenic suppressor cell populations. Cell. Immunol., 60: 287-297, 1981.

[14] 14. OPELZ, G. & SCHEER, M. - Cutaneous sensitivity and in vitro responsiveness of lymphocytes in patients with disseminated coccidioidomycosis, J. infect. Dis., 15: 360-371, 1975.

[15] 15. PAPPAGIANIS, D. - Coccidioidomicosis. In: BALOWS, A.; HANSLER, W.; OHASHI, M. & TURANO, A., ed. - Laboratory diagnosis of infectious diseases. Principles and Practice. New York, Springer Verlag, 1988. v.1, p. 677-686.

[16] 16. PETKUS, A. & BAUM, L. - Natural killer cell inhibition of young spherules and endospores of Coccidioides immitis. J. Immunol., 139: 3107-3111, 1987.

[17] 17. REMESAR, M.; BLEJER, J.; NEGRONI, R. & NEJAMKIS, M. - Cyclophosphamide effect on coccidioidomycosis in the rat. Rev. Inst. Med. trop. S. Paulo, 31: 423-429, 1989.

[18] 18. STEVENS, D. - Clinical manifestations and management of coccidioidomycosis in the compromised patient. In: WARNOCK, D. & RICHARDSON, M., ed. - Fungal infections in the compromised patient. New York, J. Willey & Sons, 1982. p. 199-205.

Brasil

Brasil

Experimental coccidioidomycosis in the immunosuppressed rat

Coccidioidomicose experimental em ratos imunossuprimidos

Abstracts

Address for correspondence:

Publication Dates

History