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Development of a new drug acting on the CD16 receptor for the treatment of autoimmune diseases and septic shock

Grant number: 17/08609-5
Support type:Scholarships abroad - Research Internship - Doctorate (Direct)
Effective date (Start): June 01, 2017
Effective date (End): December 31, 2017
Field of knowledge:Biological Sciences - Immunology
Principal Investigator:Fabiano Pinheiro da Silva
Grantee:Mario Diego Teles Correia
Supervisor abroad: Renato Costa Monteiro Filho
Home Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Local de pesquisa : Université Paris Diderot - Paris 7, France  
Associated to the scholarship:16/03665-1 - Development of a new drug acting on the CD16 receptor for the treatment of autoimmune diseases and septic shock, BP.DD

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.