Papel do eosinófilo na candidíase oral induzida em animais imunossuprimidos

• Ano de defesa: 2019
• Autor(a) principal: Jordane Clarisse Pimenta Gaggino
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Minas Gerais; Brasil; ICB - INSTITUTO DE CIÊNCIAS BIOLOGICAS; Programa de Pós-Graduação em Microbiologia; UFMG
• Palavras-chave em Português: Candidíase oral; Imunossupressão; Eosinófilos; 5-Fluorouracil; Microbiologia; Candidíase bucal; Dexametasona; Fluoruracila
• Link de acesso: http://hdl.handle.net/1843/30435

The increase in life expectancy as well as the modern lifestyle has contributed to the establishment of immunosuppressive conditions. In addition, the increased prevalence of chronic and autoimmune diseases results in increased use of corticosteroids, cytotoxic chemotherapeutics, and post-transplant immunosuppressive therapies. These treatments can compromise the immune system and trigger opportunistic infections such as candidiasis. Oral candidiasis is an opportunistic fungal infection that has increased its incidence in the last decades. It has as etiological agent fungi of the genus Candida ssp, mainly the species C. albicans. In this context, the objective of this study was to standardize models of oral candidiasis in mice immunosuppressed by corticoid dexamethasone and anti-neoplastic 5-FU in order to study the pathogenesis of the disease and the role of eosinophils in this infection. Wild mice (WT) of the C57BL/6 and BALB/c strain were used. The standardization was done to define the inoculum to be used and an infection kinetics after sublingual inoculation of C. albicans and several parameters were evaluated. Our results with dexamethasone demonstrate that C. albicans infection in immunosuppressed mice induced a lower inflammatory response to infection, demonstrated by a lower recruitment of neutrophils and macrophages to the sites of infection and increased fungal load on the tongue and spleen of the animals. The infected mice showed a significant body weight loss in relation to the control. Furthermore, we demonstrated important histopathological changes in the tongue of animals treated with 5-FU as the total loss of tissue architecture. In addition, we detonate through the use of anti-tumor 5-FU that mice are extremely immunosuppressed and susceptible to oral candidiasis, with high fungal load. We used eosinophil-deficient mice (Δdb /Gata1-/-) and found that the course of disease induced by oral infection by C. albicans associated with 5-FU treatment is milder and is associated with an improvement in the clinical and inflammatory parameters previously describe. In general, we developed two experimental models in immunosuppressed WT mice that mimic most of the parameters of clinical oral candidiasis. Furthermore, we have shown that eosinophils can often cause damage to the host against C. albicans infection. These models will contribute to the elucidation of future mechanisms associated with the pathogenesis of C. albicans-host interaction and the development of new therapeutic potentials.