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

• Grant number: 19/24440-6
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: March 01, 2020
• End date: January 31, 2023
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Flávio Vieira Loures
• Grantee: Valéria de Lima Kaminski
• Host 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 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)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

PREITE, NYCOLAS WILLIAN; KAMINSKI, VALERIA DE LIMA; BORGES, BRUNO MONTANARI; CALICH, VERA LUCIA GARCIA; LOURES, FLAVIO VIEIRA. Myeloid-derived suppressor cells are associated with impaired Th1 and Th17 responses and severe pulmonary paracoccidioidomycosis which is reversed by anti-Gr1 therapy. FRONTIERS IN IMMUNOLOGY, v. 14, p. 19-pg., 2023-01-26. (18/14762-3, 19/24440-6, 21/09962-6, 19/09278-8)

KAMINSKI, VALERIA DE LIMA; PREITE, NYCOLAS WILLIAN; BORGES, BRUNO MONTANARI; DOS SANTOS, BIANCA VIEIRA; CALICH, VERA LUCIA GARCIA; LOURES, FLAVIO VIEIRA. The immunosuppressive activity of myeloid-derived suppressor cells in murine Paracoccidioidomycosis relies on Indoleamine 2,3-dioxygenase activity and Dectin-1 and TLRs signaling. SCIENTIFIC REPORTS, v. 13, n. 1, p. 15-pg., 2023-07-18. (20/08460-4, 19/24440-6, 19/09278-8, 19/10097-8, 18/14762-3, 21/09962-6)