Investigation of the mechanisms of D6 expression in vital organs during sepsis

• Grant number: 15/21240-5
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: December 01, 2015
• End date: April 30, 2016
• Field of knowledge: Biological Sciences - Pharmacology
• Principal Investigator: Fernando de Queiroz Cunha
• Grantee: Fernanda Vargas e Silva Castanheira
• Supervisor: Gerard John Graham
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: University of Glasgow, Scotland
• Associated to the scholarship: 12/04132-6 - Role of D6 receptor in the inflammatory response development during sepsis, BP.DR

Abstract

Sepsis is a systemic inflammatory response resulted from the inability of the immune system to control infections. Neutrophils are the first cells to arrive at the infection site, and chemokines have a fundamental role in this process. These chemokines however, contribute to the systemic inflammatory response observed in sepsis. Although under physiological conditions, neutrophils do not respond to the CC subfamily of chemokines, our group has shown that during sepsis neutrophils become responsive to these chemokines. D6 is an atypical chemokine receptor that is involved with the scavenger of the CC chemokine subfamily, regulating different inflammatory processes. Therefore, we propose to FAPESP to investigate the role of D6 in the local and systemic inflammatory response during sepsis. The results obtained during the development of the current project demonstrated that D6 has a protective role during sepsis. Although we demonstrated that D6 is not involved with the control of the local inflammatory response in sepsis, this receptor has an important role in the systemic inflammatory response. In the absence of D6 there is an increase in the levels of CC chemokines in vital organs. In this way, we also demonstrated that D6 expression is increased in vital organs of wild type mice after sub-lethal sepsis, when compared to WT mice submitted to lethal CLP. This data correlates with the increased levels of CC chemokines in theses organs of mice submitted to lethal sepsis. Thus, our data indicate that D6 expression in vital organs could be important for the control of the systemic levels of chemokines, limiting the systemic inflammatory response during sepsis. In order to understand the mechanisms involved in the expression of D6 and also on its protective role during sepsis, we are setting up a collaborative study with Prof. Gerard Graham from the University of Glasgow, which is expert in field of atypical chemokine receptors, including D6. Therefore, we are applying for BEPE fellowship program to spend 5 months in his laboratory to develop this project.