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Influence of the enzyme indoleamine-2,3-dioxygenase (IDO) in the differentiation and function of dendritic cells and regulatory T cells in the pulmonary paracoccidioidomycosis of resistant and susceptible mice to P. brasiliensis infection

Grant number: 11/51258-2
Support type:Regular Research Grants
Duration: October 01, 2011 - January 31, 2014
Field of knowledge:Biological Sciences - Immunology
Principal Investigator:Vera Lucia Garcia Calich
Grantee:Vera Lucia Garcia Calich
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Paracoccidioides brasiliensis is a pathogenic fungus restricted to Latin America and its natural route of infection is the inhalation of fungal particles. In paracoccidioidomycosis (PCM), the regulatory mechanisms mediated by innate and cellular immunity are still unclear. Indoleamine 2,3-dioxygenase (IDO) is an IFN-gamma induced enzyme which catalyzes the tryptophan metabolism along the kynurenine pathway. It is known that IDO can control host-pathogen interaction by inhibiting the proliferation of intracellular microorganisms due to tryptophan starvation and by its immunosuppressive effect on T cell immunity. We have previously investigated the role of IDO in pulmonary PCM of susceptible (B10.A) and resistant (AJ) mice using control and 1-methyl-DL-tryptophan (1MT, an IDO inhibitor)-treated mice. Early in infection of susceptible mice, IDO was shown to reduce fungal loads and to decrease the number and activation of inflammatory CD4+ and CD8+ T cells that migrate to the lungs. In resistant mice, IDO controls early fungal loads, but exerts a suppressive effect on T cell immunity only at week 8 post infection. In both mouse strains IDO was shown to exert a dual role by diminishing fungal burdens but also suppressing T cell immunity due to its stimulatory effect on the expansion of regulatory T cells. This project was aimed to better study the influence of IDO on the behavior of dendritic and regulatory T cells in the course of the infection of susceptible and resistant mice. This work will clarify some important aspects on the immunosuppression associated with the severe forms of PCM and will possibly open new perspectives to the immunotherapy of this important systemic mycosis. (AU)

Scientific publications (6)
(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)
DE ARAUJO, ELISEU FRANK; PREITE, NYCOLAS WILLIAN; VELDHOEN, MARC; LOURES, FLAVIO VIEIRA; GARCIA CALICH, VERA LUCIA. Pulmonary paracoccidioidomycosis in AhR deficient hosts is severe and associated with defective Treg and Th22 responses. SCIENTIFIC REPORTS, v. 10, n. 1 JUL 9 2020. Web of Science Citations: 0.
DE ARAUJO, ELISEU FRANK; LOURES, FLAVIO VIEIRA; FERIOTTI, CLAUDIA; COSTA, TANIA; VACCA, CARMINE; PUCCETTI, PAOLO; ROMANI, LUIGINA; GARCIA CALICH, VERA LUCIA. Disease Tolerance Mediated by Phosphorylated indoleamine-2,3 Dioxygenase confers resistance to a Primary Fungal Pathogen. FRONTIERS IN IMMUNOLOGY, v. 8, NOV 13 2017. Web of Science Citations: 2.
DE ARAUJO, ELISEU FRANK; FERIOTTI, CLAUDIA; DE LIMA GALDINO, NAYANE ALVES; PREITE, NYCOLAS WILLIAN; GARCIA CALICH, VERA LUCIA; LOURES, FLAVIO VIEIRA. The IDO-Ahr axis controls Th17/Treg Immunity in a Pulmonary Model of Fungal Infection. FRONTIERS IN IMMUNOLOGY, v. 8, JUL 24 2017. Web of Science Citations: 16.
BAZAN, SILVIA B.; COSTA, TANIA A.; DE ARAUJO, ELISEU FRANK; FERIOTTI, CLAUDIA; LOURES, FLAVIO V.; PRETEL, FERNANDO D.; CALICH, VERA L. G. Loss- and Gain-of-Function Approaches Indicate a Dual Role Exerted by Regulatory T Cells in Pulmonary Paracoccidioidomycosis. PLoS Neglected Tropical Diseases, v. 9, n. 10 OCT 2015. Web of Science Citations: 4.
COSTA, TANIA A.; BAZAN, SILVIA B.; FERIOTTI, CLAUDIA; ARAUJO, ELISEU F.; BASSI, ENIO J.; LOURES, FLAVIO V.; CALICH, VERA L. G. In Pulmonary Paracoccidioidomycosis IL-10 Deficiency Leads to Increased Immunity and Regressive Infection without Enhancing Tissue Pathology. PLoS Neglected Tropical Diseases, v. 7, n. 10 OCT 2013. Web of Science Citations: 14.
BERNARDINO, SIMONE; PINA, ADRIANA; FELONATO, MAIRA; COSTA, TANIA A.; DE ARAUJO, ELISEU FRANK; FERIOTTI, CLAUDIA; BAZAN, SILVIA BOSCHI; KELLER, ALEXANDRE C.; LEITE, KATIA R. M.; CALICH, VERA L. G. TNF-alpha and CD8(+) T Cells Mediate the Beneficial Effects of Nitric Oxide Synthase-2 Deficiency in Pulmonary Paracoccidioidomycosis. PLoS Neglected Tropical Diseases, v. 7, n. 8 AUG 2013. Web of Science Citations: 15.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.