Infecção experimental por Candida spp. e tropismo para o sistema nervoso central
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Data
2018-07-30
Autores
Sanches, Marcelo D'Alessandre
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Universidade Estadual Paulista (Unesp)
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SANCHES, M. A. Infecção experimental por Candida spp. e tropismo para o sistema nervoso central. 2018. 59 p. Dissertação (Mestrado) – Faculdade de Medicina de Botucatu, Universidade Estadual Paulista (Unesp), Botucatu, 2018. O gênero Candida inclui fungos comensais que podem causar infecções locais e sistêmicas, com envolvimento frequente de órgãos vitais, incluindo o sistema nervoso central (SNC). Candida spp. ocupam o quarto lugar entre as infecções que atingem o SNC. Entre os pacientes em terapia imunossupressora, a incidência de Candida não-albicans tem aumentado tanto quanto a incidência de C. albicans. Neste contexto, o objetivo deste trabalho foi caracterizar as alterações no SNC após infecção sistêmica por espécies de Candida não-albicans em camundongos imunocompetentes e imunossuprimidos. Camundongos C57BL6, fêmeas adultas, foram infectados por via venosa com leveduras de C. glabrata, C. krusei e C. parapsilosis e imunossuprimidos com prednisolona. As três espécies de Candida disseminaram para o SNC de animais imunocompetentes. O efeito do tratamento com prednisolona foi avaliado pela variação do peso corporal, análise microbiológica e histopatológica do SNC, e produção de citocinas de células esplênicas nos 3 e 14 dias após infecção. A imunossupressão resultou na perda de peso corporal, em leucopenia e reduziu a produção de IL-2 no baço. No dia 14 após infecção, a carga fúngica diminuiu no SNC de camundongos imunocompetentes e aumentou nos imunossuprimidos. Intenso infiltrado inflamatório associado a um perfil de células Th1 foi observado em amostras de cérebro de camundongos imunossuprimidos e infectados com C. krusei, em comparação com camundongos imunocompetentes infectados. Em conjunto, esses resultados indicam que C. glabrata, C. krusei e C. parapsilosis também são capazes de se disseminarem para o SNC e promoverem inflamação local. Além disso, eles demonstraram que a corticoterapia aumenta a carga fúngica no SNC. É possível que a neuroinflamação desencadeada por Candida possa ser ainda mais deletéria quando associada a outras patologias do SNC.
SANCHES, M. A. Experimental infection by Candida spp. and tropism to the central nervous system. 2018. 59 p. Thesis (Master) – Botucatu Medical School, São Paulo State University (Unesp), Botucatu, 2018. The genus Candida includes commensal fungi that can cause local and systemic infections, with frequent involvement of vital organs, include central nervous system (CNS). Candida spp. occupy the fourth place among infections in the CNS. Among patients on immunosuppressive therapy, the incidence of Candida non-albicans has increased as much as the incidence of C. albicans. In this context, the objective of this work was to characterize the changes in the CNS after a systemic infection by non-albicans Candida species in immunocompetent and immunosuppressed mice. Adult female C57BL/6 mice were intravenously infected with C. glabrata, C. krusei and C. parapsilosis yeasts and were immunosuppressed with prednisolone. All Candida spp. disseminated to the brain and spinal cord samples from immunocompetent animals. The effect of prednisolone treatment was evaluated by body weight variation, microbiological and histopathological analysis of the CNS, and spleen cells cytokine production on days 3 and 14 post-infection. The immunosuppression resulted in body weight loss, in leukopenia and reduced IL-2 production in the spleen. At day 14 post-infection, CNS fungal load decreased in the immunocompetent mice and increased in the immunosuppressed ones. Inflammatory infiltration associated to a Th1 cells profile was higher in brain samples of C. krusei immunosuppressed compared with immunocompetent infected mice. Altogether, these results indicate that C. glabrata, C. krusei and C. parapsilosis are also able to disseminate, reach the CNS and promote local inflammation. In addition, they clearly show that corticotherapy increases fungal load in the CNS. It is possible that the neuroinflammation triggered by Candida can be even more deleterious in other CNS pathologies.
SANCHES, M. A. Experimental infection by Candida spp. and tropism to the central nervous system. 2018. 59 p. Thesis (Master) – Botucatu Medical School, São Paulo State University (Unesp), Botucatu, 2018. The genus Candida includes commensal fungi that can cause local and systemic infections, with frequent involvement of vital organs, include central nervous system (CNS). Candida spp. occupy the fourth place among infections in the CNS. Among patients on immunosuppressive therapy, the incidence of Candida non-albicans has increased as much as the incidence of C. albicans. In this context, the objective of this work was to characterize the changes in the CNS after a systemic infection by non-albicans Candida species in immunocompetent and immunosuppressed mice. Adult female C57BL/6 mice were intravenously infected with C. glabrata, C. krusei and C. parapsilosis yeasts and were immunosuppressed with prednisolone. All Candida spp. disseminated to the brain and spinal cord samples from immunocompetent animals. The effect of prednisolone treatment was evaluated by body weight variation, microbiological and histopathological analysis of the CNS, and spleen cells cytokine production on days 3 and 14 post-infection. The immunosuppression resulted in body weight loss, in leukopenia and reduced IL-2 production in the spleen. At day 14 post-infection, CNS fungal load decreased in the immunocompetent mice and increased in the immunosuppressed ones. Inflammatory infiltration associated to a Th1 cells profile was higher in brain samples of C. krusei immunosuppressed compared with immunocompetent infected mice. Altogether, these results indicate that C. glabrata, C. krusei and C. parapsilosis are also able to disseminate, reach the CNS and promote local inflammation. In addition, they clearly show that corticotherapy increases fungal load in the CNS. It is possible that the neuroinflammation triggered by Candida can be even more deleterious in other CNS pathologies.
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Palavras-chave
candidíase sistêmica, imunossupressão, infecção experimental, resposta imune periférica, sistema nervoso central, systemic candidiasis, immunosuppression, experimental infection, peripheral immune response, central nervous system