Manipulation of natural process and enhancement of cell antibacterial activity against advanced sepsis

Septicemia is an acute systemic infection in which human body is invaded into blood circulation by pathogenic bacteria or conditional pathogenic bacteria, grows and propagates in blood and produces toxin For a long time, there has been no effective treatment for advanced sepsis Researchers at Ohio State University have developed a cell therapy to support a fragile immune system against sepsis They used nanotechnology to transform healthy immune cells into drugs with stronger bactericidal ability The modified immune cells removed bacteria from the blood and main organs of mice, greatly improving their survival rate The study was published in Nature Nanotechnology on January 6, 2020 Macrophage is one of the earliest responders in the immune system Its job is to "eat" the invading pathogens However, in septic patients, the number of macrophages and other immune cells is lower than the normal level and cannot play the normal function In this study, the researchers first collected monocytes from the bone marrow of healthy mice and then cultured them into macrophages The laboratory also developed vitamin based nanoparticles, which are particularly good at delivering messenger RNA, and constructed messenger RNA encoding antimicrobial peptides and signaling proteins, which can make antimicrobial peptides accumulate specifically in lysosomes inside macrophages, which is the key to bacterial killing activity The researchers then transported nanoparticles loaded with messenger RNA to the macrophages they produced with donor monocytes, from which they had cells "make" new therapies Because macrophages have antibacterial activity naturally, if other antimicrobial peptides are added to cells, the antibacterial activity can be further enhanced and the whole macrophage can be cleaned up of bacteria Schematic diagram of chemical structure of adoptive macrophage transfer and vitamin derived lipids The researchers then treated the mice with cells The septic mice in this study were infected with multi drug resistant Staphylococcus aureus and Escherichia coli, and their immune system was inhibited Each treatment consisted of about 4 million engineered macrophages The control group consisted of normal macrophages and placebo Compared with the control group, the treatment can significantly reduce the number of bacteria in the blood after 24 hours For the remaining bacteria in the blood, the second treatment can remove them Immunosuppressive effect of mac-bmdms on septic mice induced by mixed MDR bacteria This work focuses on the treatment of advanced sepsis, provides another strategy to overcome the sepsis caused by multi drug resistant bacteria, and opens up the possibility of developing nanoparticle cell therapy for infectious diseases Researchers are working with clinicians specializing in sepsis treatment to accelerate the drug development process.