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The role of Myeloid-Derived Suppressor Cells (MDSCs) in Murine Paracoccidioidomycosis

Grant number: 19/09278-8
Support type:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): July 01, 2019
Effective date (End): June 30, 2023
Field of knowledge:Biological Sciences - Immunology
Principal Investigator:Flávio Vieira Loures
Grantee:Nycolas Willian Preite
Home Institution: Instituto de Ciência e Tecnologia (ICT). Universidade Federal de São Paulo (UNIFESP). Campus São José dos Campos. São José dos Campos , SP, Brazil
Associated research grant:18/14762-3 - Immunosuppression in paracoccidioidomycosis: the regulatory role of myeloid-derived suppressor cells (MDSCs) on host immunity, tissue pathology and genetic adaptation of fungal cells, AP.JP2

Abstract

Previous studies in Paracoccidioidomycosis (PCM), the most prevalent Systemic Mycosis in Latin America, revealed that immunity of hosts is tightly regulated by several suppressive mechanisms mediated by tolerogenic plasmacytoid dendritic cells, the enzyme 2, 3 indoleamine dioxygenase (IDO1) and regulatory T cells (Treg). IDO1 was also seen to orchestrate local and systemic immunosuppressive effects through the recruitment and activation of Myeloid-Derived Suppressor Cells (MDSCs), a heterogeneous population of myeloid cells with a potent ability to suppress T cell responses. These cells regulate immune responses and tissue repair in healthy individuals and rapidly expands during infection. The involvement of MDSC during PCM was never investigated, leading us to propose this study that aims to characterize the participation of MDSCs in the immunity against P. brasileinsis infection. The presence, phenotype and activity of MDSCs will be evaluated at several post infection periods. In addition, the disease severity and several features of the immune response will be assessed in MDSC-depleted and non-depleted C57BL/6 mice using a specific monoclonal antibody. A better understanding of immunoregulation in pulmonary PCM, mediated by MDSCs will possibly advance the current knowledge of the host-pathogen responses that control the severity of PCM and will open new perspectives for more effective therapies. (AU)