CD16 blockade as a new therapeutic strategy against Lupus and in Escherichia coli-induced sepsis

• Grant number: 16/05307-5
• Support Opportunities: Regular Research Grants
• Start date: October 01, 2016
• End date: September 30, 2018
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Irineu Tadeu Velasco
• Grantee: Irineu Tadeu Velasco
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Fabiano Pinheiro da Silva ; Marcel Cerqueira Cesar Machado

Abstract

Development of new drug acting on the CD16 receptor for the treatment of autoimmune diseases and septic shock Introduction: Despite half a century of research, sepsis is still a major cause of death in intensive care units, and constant source of concern throughout the world, mainly due to the high morbidity and mortality rates. Likewise, lupus provides tremendous cost to the individual and public health. The treatment of these two conditions is a challenge and continues to be difficult due to numerous interfering factors. A study from our group demonstrated that Escherichia coli(E. coli) is capable of binding to the CD16 receptor independently of opsonin, leading to an increase in the inflammatory response and inhibition of its own phagocytosis. Using Phage Display, we identified two peptides that obtained interaction with CD16. After the selection of peptides, we have identified an E. coli membrane protein having high similarity to our selected peptides. Objective and Methodology: We will treat sepsis in mice, induced by the cecal ligation puncture model, with antibodies against the peptides identified, in order to block the interaction of these peptides with the CD16 receptor, thus increasing the phagocytosis of bacteria E.coli. Similarly, we will treat mice with pristane-induced lupus, with these same antibodies in order to block mechanisms of inflammation and autoimmunity. Conclusion: This treatment is presented as a new therapeutic approach to sepsis caused by E. coli bacteria and perhaps other pathogens, as for autoimmune diseases. (AU)