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Master's Dissertation
DOI
https://doi.org/10.11606/D.42.2018.tde-19022018-162224
Document
Author
Full name
Nayane Alves de Lima Galdino
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2017
Supervisor
Committee
Calich, Vera Lucia Garcia (President)
Basso, Alexandre Salgado
Benard, Gil
Castoldi, Angela
Title in Portuguese
Avaliação do papel das células T reguladoras na imunomodulação da paracoccidiodomicose pulmonar estabelecida.
Keywords in Portuguese
DEREG
Imumomudulação
Paracoccidioidomicose
T reguladoras
Abstract in Portuguese
Tem sido demonstrada a grande importância dos linfócitos T reguladores (Treg) na manutenção da tolerância e no controle da resposta imune em infecções. Na paracoccidioidomicose, micose sistêmica causada pelo Paraccoccidioides brasiliensis (Pb), a atuação das células Treg tem sido estudada. Utilizando o modelo murino DEREG, foram realizadas depleções com toxina diftérica (DT) na doença estabelecida. A gravidade da doença foi avaliada 6 e 10 semanas pós infecção com Pb através da carga fúngica nos tecidos, desenvolvimento de imunidade TCD8+ e TCD4+ e histopatologia. Animais DEREG tratados com a DT apresentaram menor número de células Treg, menor carga fúngica no pulmão, fígado e baço e redução dos granulomas comparados ao controle (PBS). Observou-se também um maior influxo de células TCD4+ e TCD8+ efetoras nos pulmões dos camundongos tratados com DT e aumento na produção de citocinas dos tipos Th1 e Th17. Portanto, demonstramos efeitos benéficos da depleção de Treg na PCM já estabelecida, caracterizado pela menor carga fúngica e maior ativação da imunidade celular.
Title in English
Immunomodulatory function of regulatory T cells during pulmonary paracoccidioidomycosis.
Keywords in English
DEREG
Immunomodulation
Paracoccidiomycosis
Treg cells
Abstract in English
The great importance of regulatory T lymphocytes (Treg) has been demonstrated in maintaining tolerance and not controlling the immune response in infections. In paracoccidioidomycosis, systemic mycosis caused by Paraccoccidioides brasiliensis (Pb), the action of Treg cells has been studied. Using the DEREG murine model, depletions were performed with diphtheria toxin (DT) in the established disease. The severity of the disease was assessed 6 and 10 weeks post-infection with fungal load in tissues, development of TCD8+ and TCD4+ immunity and histopathology. DEREG animals treated with DT presented lower number of Treg cells, lower fungal load in the lung, liver and spleen and reduction of granulomas compared to control (PBS). There was also a greater influx of effector CD4+ and TCD8+ cells in the lungs of DT-treated mice and increased production of Th1 and Th17 cytokines. Therefore, we demonstrated beneficial effects of Treg depletion on PCM already established, characterized by lower fungal load and greater activation of cellular immunity.
 
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Publishing Date
2018-02-19
 
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