The role of ectonucleotidase CD39 in the establishment of sepsis-induced immunosuppression

• Grant number: 15/25974-3
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Effective date (Start): April 30, 2016
• Effective date (End): April 29, 2017
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: José Carlos Farias Alves Filho
• Grantee: Daniele Carvalho Bernardo Nascimento
• Supervisor: Bernhard Ryffel
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Research place: Université d'Orléans, France
• Associated to the scholarship: 12/10100-0 - The role of ectonucleotidases and adenosine in the establishment of sepsis-induced immunosuppression, BP.PD

Abstract

Immunosuppression has been shown to be one of the major long-term sequels of sepsis survivors, which is mainly characterized by the expansion of regulatory T cells (Tregs). However, the mechanisms underlying this Treg expansion remain poor understood. There are evidences showing that extracellular adenosine can induce Tregs differentiation thought activation of adenosine receptor A2a (A2aR). Interestingly, results obtained during the development of this current project show that pharmacological blockade or genetic deficiency of A2aR reduce the expansion of Tregs and improve the resistance of sepsis-surviving mice against a secondary infection challenge, suggesting that extracellular adenosine is involved, at least in part, with the development of sepsis-induced immunosuppression. The degradation of extracellular ATP by sequential activities of two ectonucleotidases, CD39 and CD73, has been considered as the main pathway for extracellular adenosine production, implicating these enzymes as potential components of sepsis-induced immunosuppression. In order to give continuity to our project, we have set up a collaborative study with Prof. Bernhard Ryffel from CNRS in France to investigate the role of CD39 in the development of sepsis-induced immunosuppression. Therefore, we are applying for BEPE fellowship program to spend 1 year in the laboratory of Prof. Ryffel to develop this project. (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)

NASCIMENTO, DANIELE CARVALHO; VIACAVA, PAULA RAMOS; FERREIRA, RAPHAEL GOMES; DAMACENO, MARINA ALVES; PINEROS, ANNIE ROCIO; MELO, PAULO HENRIQUE; DONATE, PAULA BARBIM; TOLLER-KAWAHISA, JULIANA ESCHER; ZOPPI, DANIEL; VERAS, FLAVIO PROTASIO; et al. Sepsis expands a CD39(+) plasmablast population that promotes immunosuppression via adenosine-mediated inhibition of macrophage antimicrobial activity. IMMUNITY, v. 54, n. 9, p. 2024+, SEP 14 2021. (13/08216-2, 15/25974-3, 12/10100-0, 15/25364-0)