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Doctoral Thesis
DOI
https://doi.org/10.11606/T.42.2009.tde-19102009-170222
Document
Author
Full name
Renata Scavone de Oliveira
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2009
Supervisor
Committee
Burger, Eva (President)
Faccioli, Lucia Helena
Martinez, Roberto
Mauro, Eliana Faquim de Lima
Verinaud, Liana Maria Cardoso
Title in Portuguese
Paracoccidioidomicose: acompanhamento de parâmetros de imunidade adquirida e do estado de ativação de fagócitos em camundongos isogênicos suscetíveis submetidos à terapia antifúngica.
Keywords in Portuguese
Anfotericina B
Antifúngicos
Imunologia
Macrófagos
Modelo murino isogênico
Neutrófilos
Paracoccidioidomicose
Receptor Toll-like 4
Abstract in Portuguese
Os efeitos da administração de anfotericina B a camundongos suscetíveis ao P. brasiliensis foram avaliados. A L-AmB reverte o padrão de suscetibilidade para o de resistência de forma mais eficiente do que a c-AmB, como observado na quantificação de UFC, NO e IgG2b. Porém, os níveis de TNF-a, IL-12, IFN-g, GM-CSF, IgG total, IgM, IgG1, IgG2a e IgA não são significativamente alterados. Neutrófilos e macrófagos peritoneais co-cultivados com Pb e L-AmB tendem a apresentar maior capacidade fungicida, mas não maior síntese de mediadores. O melhor desempenho de L-AmB poderia se dever a sua interação com TLR4. Em TLR4-deficientes ou não, a progressão da doença é similar. A eficácia da terapia, porém, é menor nos deficientes, como observado na quantificação de UFC; os perfis leucocitários e as concentrações de NO, TNF-a, IL-12 e GM-CSF não são significativamente alterados. Logo, a droga é capaz de reverter os parâmetros micológicos, mas não os imunológicos. A interação entre TLR4, P. brasiliensis e L-AmB não parece ser importante para o estabelecimento da imunidade.
Title in English
Paracoccidioidomycosis: follow up of acquired immunity parameters and of the activation state of phagocytes in susceptible isogenic mice submitted to the antifungal therapy.
Keywords in English
Amphotericin B
Antifungals
Immunology
Isogenic murine model
Macrophages
Neutrophils
Paracoccidioidomycosis
Tool-Like receptor 4
Abstract in English
Amphotericin B effects in mice susceptible to P. brasiliensis were evaluated. L-AmB reverts the susceptibility pattern to the resistant one with more efficiency than c-AmB, as confirmed by the CFU, NO e IgG2b quantifications. However, TNF-a, IL-12, IFN-g, GM-CSF, total IgG, IgM, IgG1, IgG2a and IgA levels are not significantly altered. Neutrophils and macrophages cocultivated with Pb e L-AmB tend to present higher fungicidal ability, but not enhanced synthesis of mediators. The better performance of L-AmB could be due to its interaction with TLR4. In TLR4-deficient or sufficient mice, progression of the disease is similar. The efficiency of the therapy, however, is lower in deficient animals, as seen on CFU; leukocyte profiles and NO, TNF-a, IL-12 and GM-CSF levels are not significantly altered by L-AmB-TLR4 interaction. Therefore, the drug administration is capable of reverting mycological parameters, but not the immunological ones. Interaction between TLR4, P. brasiliensis and L-AmB does not seem to play a special role in the establishment of immunity.
 
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Publishing Date
2009-12-04
 
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