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

• Grant number: 15/14283-0
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date until: September 11, 2015
• End date until: March 01, 2016
• Field of knowledge: Biological Sciences - Pharmacology
• Principal Investigator: José Carlos Farias Alves Filho
• Grantee: Raphael Gomes Ferreira
• Supervisor: Francesca Fallarino
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: Università degli Studi di Perugia, Italy
• Associated to the scholarship: 12/11312-0 - Role of enzyme indoleamine 2, 3-dioxygenase (IDO) in the development of sepsis-induced immunosuppression, BP.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 remain poor understood, but it is known that an increase in the number of regulatory T lymphocytes (Tregs) is involved in the maintenance of this state. 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 bacterial components, such as lipopolysaccharide (LPS) and CpG, as well as interferons (IFN)-±, ² and Ò. When activated, IDO initiates the kynurenine pathway of tryptophan degradation, which has been implicated in promoting Treg generation. 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 IDO on Treg development; and c) role of IDO in the susceptibility to secondary infection in animals that survive sepsis.