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Role of enzyme indoleamine 2, 3-dioxygenase (IDO) in the development of sepsis-induced immunosuppression

Grant number: 12/11312-0
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): November 01, 2012
Effective date (End): October 31, 2016
Field of knowledge:Biological Sciences - Pharmacology - General Pharmacology
Principal Investigator:José Carlos Farias Alves Filho
Grantee:Raphael Gomes Ferreira
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated scholarship(s):15/14283-0 - Role of enzyme Indoleamine 2, 3-dioxygenase (IDO) in the development of sepsis-induced immunosuppression, BE.EP.DR

Abstract

Sepsis is a systemic inflammatory response generated as a result of an infection, often leading to the development of a framework of delayed immunosuppression which may continue for years after the patient was released from hospital. The mechanisms involved in the development of sepsis-induced immunosuppression are not yet fully understood, but it is known that an increase in the number of regulatory T lymphocytes (Tregs) is involved in the maintenance of immunosuppression. The increase in Tregs is, at least in part, related to M2 macrophage activity, once unpublished results from our laboratory show that factors released from M2 macrophages may promote Treg differentiation from naïve T cells. Moreover, some works have shown tolerogenic and immunomodulatory roles for the enzyme indoleamine 2,3-dioxygenase (IDO). This enzyme is expressed in different cells of the immune system, including macrophages and dendritic cells, after activation by inflammatory cytokines like interferons and IL-27. When activated, IDO acts on substrates like tryptophan, leading to Kinurenine production. In this way, both tryptophan depletion or kinunerine production are involved in Tregs differentiation. Despite the role of IDO on immune system regulation, there are no studies in literature about its role in the development of sepsis-induced immunosuppression. Thus, this project aims to investigate: a) the IDO expression during immunosuppression development; b) the role of interferons and IL-27 on IDO expression; c) the role of IDO on M2 macrophage and Treg development; and d) role of IDO in the susceptibility to secondary infection in animals that survive sepsis.

Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
FERREIRA, Raphael Gomes. Role of enzyme Indoleamine 2, 3-dioxygenase (IDO) in the development of sepsis-induced immunosuppression. 2016. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto Ribeirão Preto.

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