The role of indoleamine 2, 3-dioxygenase 1 (IDO-1) in immunosuppressive mechanisms of myeloid-derived suppressor cells (MDSCs) in Pulmonary Paracoccidioidomycosis

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 MDSCs 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. Based on previous studies that established a positive correlation between IDO activity and MDSC infiltration we also intend to do a comparative study on MDSCs function in pulmonary PCM using IDO-deficient and sufficient-mice. 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)