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Natural killer cell activity in experimental paracoccidioidomycosis of the Syrian hamster

Atividade de células natural killer na paracoccidioidomicose experimental do hamster

Abstracts

The study evaluated the activity of NK cells during the course of experimental infection of hamsters with Paracoccidioides brasiliensis. Eigthy hamsters were infected with P. brasiliensis by intratesticular route and sacrificed at 24h, 48h, 96h, 1, 2, 4, 8 and 11 weeks of infection and compared to 40 noninfected hamsters employed as controls. These animals were submitted to the study of NK cytotoxic activity by a single-cell assay and humoral immune response by immunodiffusion and ELISA tests. The production of macrophage migration inhibitory factor in the presence of Phyto-hemagglutinin and P. brasiliensis antigen and histopathology of the lesions were evaluated at 1, 4, 8 and 11 weeks of infection. The infected animals displayed significantly high levels of NK activity during the four weeks of infection that decreased from the 8th week on when compared to controls. This impairment of NK activity was associated with depression of cell-mediated immune response and with increase in the extension of the histopathologic lesions. There was an inverse correlation between NK cell activity and specific antibody levels. The results suggest that after initial activation, NK cells were unable to control the fungus dissemination. The impairment of NK activity in the late stages of the infection might be related to immunoregulatory disturbances associated with paracoccidioidomycosis.

Paracoccidioidomycosis; Hamster; Cell-mediated immunity; NK cell activity; Antibodies


Com o objetivo de avaliar a atividade de células natural killer na paracoccidioidomicose experimental do hamster, 80 hamsters foram infectados por via intratesticular com Paracoccidioides brasiliensis e sacrificados após 24h, 48h, 96h, 1, 2, 4, 8 e 11 semanas de infecção. Como controle foram avaliados 40 hamsters normais, não infectados. Os animais foram submetidos ao estudo da atividade citotóxica de células NK pela técnica de "single-cell assay" e da resposta imune humoral pelas técnicas de imunodifusão dupla e Elisa. A produção do fator inibidor da migração de macrófagos em presença de Phytohemaglutinina e antígeno de P. brasiliensis e a histopatologia das lesões foram estudadas após 1,4, 8e 11 semanas de infecção. Os animais infectados, quando comparados aos controles, apresentaram níveis de atividade NK significativamente elevados durante as 4 primeiras semanas de infecção, havendo diminuição dessa atividade a partir da 8ª semana. Foi observada correlação inversa entre atividade NK e níveis de anticorpos específicos e, associação entre diminuição da atividade NK, depressão de resposta imune celular e aumento da extensão das lesões histopatológicas. Os resultados sugerem que após ativação inicial, as células NK são incapazes de controlar a disseminação do fungo pelos tecidos. A depressão da atividade NK na fase tardia da infecção parece estar relacionada com os distúrbios imunorregulatórios associados à paracoccidioidomicose.


IMMUNOLOGY

Natural killer cell activity in experimental paracoccidioidomycosis of the Syrian hamster

Atividade de células natural killer na paracoccidioidomicose experimental do hamster

Maria Terezinha Serrão PeraçoliI; Maria Rita Parise FortesI; Maria Flávia Pereira da SilvaI; Mário Rubens MontenegroII

IDepartamento de Microbiologia e Imunologia, IB-UNESP, Botucatu-SP

IIDepartamento de Patologia, Faculdade de Medicina de Botucatu, UNESP, Botucatu-SP

Correspondence to Correspondence to: Dra. Maria Terezinha Serrão Peraçoli Departamento de Microbiologia e Imunologia, Instituto de Biociências, UNESP 18618-000 Botucatu, SP, Brazil

SUMMARY

The study evaluated the activity of NK cells during the course of experimental infection of hamsters with Paracoccidioides brasiliensis. Eigthy hamsters were infected with P. brasiliensis by intratesticular route and sacrificed at 24h, 48h, 96h, 1, 2, 4, 8 and 11 weeks of infection and compared to 40 noninfected hamsters employed as controls. These animals were submitted to the study of NK cytotoxic activity by a single-cell assay and humoral immune response by immunodiffusion and ELISA tests. The production of macrophage migration inhibitory factor in the presence of Phyto-hemagglutinin and P. brasiliensis antigen and histopathology of the lesions were evaluated at 1, 4, 8 and 11 weeks of infection. The infected animals displayed significantly high levels of NK activity during the four weeks of infection that decreased from the 8th week on when compared to controls. This impairment of NK activity was associated with depression of cell-mediated immune response and with increase in the extension of the histopathologic lesions. There was an inverse correlation between NK cell activity and specific antibody levels. The results suggest that after initial activation, NK cells were unable to control the fungus dissemination. The impairment of NK activity in the late stages of the infection might be related to immunoregulatory disturbances associated with paracoccidioidomycosis.

Keywords: Paracoccidioidomycosis; Hamster; Cell-mediated immunity; NK cell activity; Antibodies.

RESUMO

Com o objetivo de avaliar a atividade de células natural killer na paracoccidioidomicose experimental do hamster, 80 hamsters foram infectados por via intratesticular com Paracoccidioides brasiliensis e sacrificados após 24h, 48h, 96h, 1, 2, 4, 8 e 11 semanas de infecção. Como controle foram avaliados 40 hamsters normais, não infectados. Os animais foram submetidos ao estudo da atividade citotóxica de células NK pela técnica de "single-cell assay" e da resposta imune humoral pelas técnicas de imunodifusão dupla e Elisa. A produção do fator inibidor da migração de macrófagos em presença de Phytohemaglutinina e antígeno de P. brasiliensis e a histopatologia das lesões foram estudadas após 1,4, 8e 11 semanas de infecção. Os animais infectados, quando comparados aos controles, apresentaram níveis de atividade NK significativamente elevados durante as 4 primeiras semanas de infecção, havendo diminuição dessa atividade a partir da 8ª semana. Foi observada correlação inversa entre atividade NK e níveis de anticorpos específicos e, associação entre diminuição da atividade NK, depressão de resposta imune celular e aumento da extensão das lesões histopatológicas. Os resultados sugerem que após ativação inicial, as células NK são incapazes de controlar a disseminação do fungo pelos tecidos. A depressão da atividade NK na fase tardia da infecção parece estar relacionada com os distúrbios imunorregulatórios associados à paracoccidioidomicose.

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ACKNOWLEDGEMENTS

The authors are grateful to Mr. Antonio Emilio de Oliveira, Mrs. Maria Antonia M. da Palma and Mr. Luis Alquati for technical assistance and to Dr. Paulo Curi for the statistical analysis. This study was supported by FUNDUNESP, grant 082/92 DFP.

Recebido para publicação em 23/08/1994

Aceito para publicação em 21/02/1995

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  • Correspondence to:

    Dra. Maria Terezinha Serrão Peraçoli
    Departamento de Microbiologia e Imunologia, Instituto de Biociências, UNESP
    18618-000 Botucatu, SP, Brazil
  • Publication Dates

    • Publication in this collection
      22 Feb 2007
    • Date of issue
      Apr 1995

    History

    • Accepted
      21 Feb 1995
    • Received
      23 Aug 1994
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