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Doctoral Thesis
DOI
https://doi.org/10.11606/T.42.2013.tde-18062013-102750
Document
Author
Full name
Julian Esteban Muñoz Henao
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2013
Supervisor
Committee
Taborda, Carlos Pelleschi (President)
Almeida, Sandro Rogerio de
Barros, Mário Henrique de
Rodrigues, Elaine Guadelupe
Rodrigues, Marcio Lourenço
Title in Portuguese
Avaliação do peptídeo sintético (P10): associado ao tratamento quimioterápico em camundongos BALB/c anérgicos infectados com Paracoccidioides brasiliensis.
Keywords in Portuguese
Antifúngicos
Imunosupressão
Linfócitos T
Paracoccidioidomicose
Sistema imune
Vacinas
Abstract in Portuguese
A paracoccidioidomicose (PCM), doença sistêmica de caráter granulomatoso, é causada pelo fungo termodimórfico Paracoccidioides brasiliensis (Pb). A gp43 secretada pelo Pb, possui um trecho específico de 15 aminoácidos designado como (P10), é reconhecido por linfócitos T. No presente trabalho, avaliamos a ativação da resposta imune e o efeito aditivo da imunização com o peptídeo P10, em camundongos induzidos à imunossupressão com dexametasona. Os resultados indicam um efeito aditivo da imunização com P10 e o tratamento com as drogas em camundongos BALB/c imunossuprimidos e infectados; associado a redução da carga fúngica no pulmão, baço e fígado desses animais, detectamos aumento de citocinas proinflamatorias, no homogenato de pulmão e no sobrenadante de cultura celular. Animais imunossuprimidos e imunizados com P10 apresentaram um aumento significativo na produção de Óxido Nítrico (NO). A eficiencia na resposta levou a um aumento na sobrevida de 100%. Estes resultados sugerem que o P10, representa uma alternativa promisoria na geração de uma vacina anti-PCM.
Title in English
Assessment of synthetic peptide (P10): associated with chemotherapy treatment in BALB/c mice infected with Paracoccidioides brasiliensis.
Keywords in English
Antifungals
Immune system
Immunosuppression
Paracoccidioidomycosis
T lymphocytes
Vaccines
Abstract in English
Paracoccidioidomycosis (PCM) is a systemic granulomatous disease caused by Paracoccidioides brasiliensis (Pb). The gp43 secreted by Pb has a 15-mer peptide designated as P10 that is recognized by T lymphocytes. In the present work we evaluated the activation of immune response and the additive effect of P10 immunization in BALB/c mice induzed to immunossupression with Dexamethasone. Results indicate an additive effect of P10 immunization and the treatment with drugs in BALB/c mice immunosuppressed and infected; associated with a significant reduction in fungal burden in the lung, spleen and liver of these animals. Also, we detected an increase of proinflammatory cytokines such as IFN-g, TNF-a e IL-12, in lung homogenates and cell culture supernatant. Immunosuppressed animals that were immunized with P10 showed an increase in the Nitric Oxide production. The efficiency of response led to a 100% survival in animals immunized with P10 and treated with antifungal drugs. Our results suggest that P10 represents a promising alternative of anti-PCM vaccine generation.
 
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Publishing Date
2013-10-01
 
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