Preparation of Anti Toll-Like Receptor-4 Nano-Antibody and Its Effect on Gram Negative Sepsis

The essence of sepsis is the excessive immune response caused by infectious factors, which leads to the release of a large number of inflammatory factors and the injury of tissues and organs. Once the reaction is triggered, it will develop according to its own rules, and it does not depend on infection factors. The occurrence and severity of sepsis depend entirely on the reaction of the body. When pathogens invade the body, they rely on pattern recognition receptors to play a defensive role, TLR4 is the main switch of innate immunity. The current research shows that LPS can induce the up-regulation of TLR4 gene expression in monocytes, neutrophils and other immune cells. The upregulated TLR4, as a new receptor, mediates more cell activation and the release of inflammatory mediators. Under this positive feedback, the inflammatory response is constantly amplified, which eventually leads to the development of sepsis. In this study, TLR4 extracellular domain antigen was obtained by protein expression and purification, and anti-TLR4 C-terminal and intermediate domain nano-antibody was obtained by phage display antibody library preparation technology. In vitro and in vivo experiments confirmed that anti-TLR4 nano-antibody can effectively reduce the release of inflammatory factors and improve the survival rate of animals, while the C-terminal and intermediate domain are closed at the same time, the effect is more obvious. The clinical treatment of sepsis provides new ideas and strategies.