The thymus is the primary lymphoid organ responsible for the development and maturation of T lymphocytes. To perform such role, the thymic microenvironment needs to be intact, and there should be a fine control of chemokines and growth factors released by epithelial cells, thymic dendritic cells and macrophages. However, the thymus can suffer involution under physiological conditions, e.g. in aging and pathologies, such as infections. Studies from our laboratory have shown that experimental infection with Paracoccidioides brasiliensis, the causative agent of the most prevalent systemic mycosis in South and Central America - the paracoccidioidomycosis, induces thymic atrophy, with loss of corticomedullary delimitation, depletion of cortical thymocytes, decreased ability in migration with retention of double-negative thymocytes, and the presence of inflammatory infiltrate composed of neutrophils and macrophages. The thymic atrophy observed may be related to (i) changes in the compartments of thymic stromal cells, (ii) increased death of thymocytes and (iii) premature migration of thymocytes to the periphery. Recently, the involvement of NLRP3 inflammasomes, macromolecular complexes involved in the inflammatory activation of caspases, has been suggested as essential in eliminating various pathogens and may be involved in thymic atrophy triggered by physiological aging. Thus, this project aims to analyze the early thymic atrophy observed during experimental infection with Paracoccidioides brasiliensis, the possible cell death pathways involved in the loss of thymocytes and the involvement of inflammatory pathways in this process, with emphasis on inflammasome NLRP3.
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