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GALDINO, N. A. L. Immunomodulatory function of regulatory T cells during pulmonary paracoccidioidomycosis. 2017. 78 f. Master thesis (Immunology) Instituto de Ciências Biomédicas, Universidade de São Paulo, 2017. The importance of regulatory T cells (Treg) in maintaining tolerance to self antigens and controlling the immune response in various infections has been recently demonstrated. In many infectious diseases, Treg cells suppressive activity of the effector immune response has been associated with deleterious effects, however in other models this activity has been considered protective in order to control excessive inflammation and tissue pathology. In paracoccidioidomycosis (PCM), the most frequent systemic mycosis in Latin America caused by Paraccoccidioides brasiliensis (Pb), the role of Treg cells role in the infection has been recently studied. We used C57BL/6 transgenic mice for expression of the diphtheria toxin receptor (DTR) and GFP ("green fluorescent protein") under the influence of FoxP3 gene transcription factor, which is characteristic of Treg cells. Depletion was performed by treatment of C57BL/6 (DEREG) mice with diphtheria toxin after 3 weeks of infection with a million yeast by intratracheal surgery. Disease severity was assessed 6 weeks after the infection by characterizing the tissue fungal burden, CD8 immune development, CD4 (Th1/Th2/Th17) and histopathology. Over the infection period, DEREG mice treated with diphtheria toxin showed smaller number of Treg cells, which was associated with a lower fungal burden in the lung, liver and spleen, less tissue damage and reduced granulomas when compared to control mice (infected and treated saline). Additionally, we observed a greater influx of CD4 and CD8 effector cells in the lungs of DEREG mice followed by significant increase in cytokine production in Th1 and Th17 cell types when compared to control animals. Thus, this data indicates beneficial effects of depletion of regulatory T cells in PCM already established, for the first time. All results showed an improvement of the disease characterized by decreased in fungal burden and increased activation of CD4 immunity and CD8. More importantly, these findings highlight a immunotherapeutic treatment perspective for established PCM through immunomodulation of Treg cells, controlling the number and function of these population.

Avaliação do papel das células T reguladoras na imunomodulação da paracoccidiodomicose pulmonar estabelecida.