Nature: Super-magical new immune mechanism! Scientists have discovered for the first time that ordinary cells release exosomes as bait to trap and neutralise the lethal toxin seditoids released by superbugs.

I don't know how many Magic Secrets of the human body are waiting for scientists to discover.not long ago, the research team led by Ken H. Cadwell and Victor J. Torres of New York University School of medicine, published in the top journal Nature [1], once again refreshed my understanding of human innate immunity.they found that human cells, after discovering the DNA of super drug-resistant bacteria, secreted the protein on the cell membrane surface that could be bound by bacterial toxins in the form of exosomes.in this way, the killer toxin released by the superbacteria is trapped by exosomes, and the cells are saved.I have to say that our human body cells are extremely clever in this way of "gecko tail cutting".the researchers believe that they may have found a new innate immune mechanism against bacterial infection [2].} the battle between bacteria and cells: yellow is exosomes, purple is toxins, blue is bacteria, methicillin-resistant Staphylococcus aureus (MRSA) is a common super bacteria, which has resistance to many antibiotics.it can form toxins (PFTs) through the secretory channels to destroy the host cell membrane, resulting in host cell death [3].however, the researchers observed that about one fifth of people in the United States have MRSA, but very few people die of MRSA infection, about one in ten thousand [4].this prompted Cadwell and Torres to think: is there a innate immune mechanism in the human body that can neutralize the formation of toxins in the pore channels? (source: med.nyu.edu ）Based on previous studies, Cadwell and Torres have known that the pore forming toxin secreted by bacteria will bind with ADAM10 on the cell surface, resulting in cell membrane perforation [5].however, five years ago, Cadwell and Torres jointly discovered that the autophagy protein Atg16L1 can protect cells from MRSA pore forming toxin (α - toxin) [6].what is the relationship between Atg16L1, ADAM10 and pore forming toxin? Is there a little-known innate immune mechanism hidden behind it? To understand the above two problems, we must first clarify the relationship between Atg16L1 and ADAM10 in cells.} Ken H. Cadwell (source: med.nyu.edu ）Cadwell and Torres team first inhibited the expression of Atg16L1 gene in human alveolar epithelial cell line. As a result, the expression level of ADAM10 was increased.cells with low Atg16L1 gene expression were treated with purified α - toxin, resulting in a large number of cell death; while cells with ADAM10 gene expression inhibited were resistant to α - toxin.this result indicates that the expression of ADAM10 is negatively regulated by Atg16L1.in short, Atg16L1 makes cells resistant to MRSA secreted α - toxins by reducing the number of ADAM10 on the cell surface.how does this process happen? Since Atg16L1 is an autophagy protein, the autophagy that researchers first thought of, namely Atg16L1, modulates the autophagy pathway and degrades ADAM10. however, Cadwell and his colleagues found that Atg16L1 reduced ADAM10 levels, which was not associated with autophagy. } the expression of Atg16L1 and ADAM10 and the cell death rate under toxin treatment continued to consult relevant data, Cadwell team found that ATG like proteins can also promote the release of exosomes [7]. coincidentally, ADAM10 appears on exosomes with a diameter of 40nm-120nm [8]. does Atg16L1 allow cells to release ADAM10 on the surface of exosomes? Cadwell and his colleagues quickly turned around and analyzed the presence of exosomes secreted by cells with suppressed Atg16L1 expression and normal cells. of course, the exosomes carrying ADAM10 decreased significantly after the decrease of Atg16L1 expression. and they also confirmed that Atg16L1 can reduce ADAM10 on cell surface by regulating the formation of exosomes, rather than acting on ADAM10 itself. here, the first question raised above is basically clear: Atg16L1 can reduce ADAM10 on the cell surface by promoting the formation of exosomes, thus avoiding cell damage by α - toxin. } Atg16L1 expression level was decreased and exosomes were reduced by naked eyes. Is this process regulated by bacterial infection? To solve this problem, Cadwell's team used heat to kill a variety of bacteria and then stimulated human and mouse cells with these bacteria. As a result, the secretion of exosomes increased significantly. after testing various substances in the bacteria, they determined that it was the bacterial DNA that induced the exosome secretion. experiments in mice also confirmed that bacterial treatment could not promote the production of exosomes if Atg16L1 expression was inhibited. based on this, the researchers believe that the bacterial DNA is recognized by cells, which promotes the exosome secretion process participated by Atg16L1, and finally leads to a large number of exosomes carrying ADAM10 to be secreted out of the cell. } after different bacterial treatments, the release of exosomes increased. After cells sense the existence of bacteria, do the released exosomes have defense function? The researchers isolated exosomes from low and normal Atg16L1 cell lines, and then treated alveolar epithelial cells with these exosomes and alpha toxin. results as expected, the exosomes produced by the cells with normal Atg16L1 expression had a protective effect on alveolar epithelial cells, while the exosomes with low Atg16L1 expression had no protective effect. however, when more exosomes with low Atg16L1 expression were added, the protective effect also gradually appeared. this shows again that the protective effect is determined by the number of exosomes. subsequent in vivo experiments in mice confirmed the above process again. in addition, the researchers also found that exosomes secreted by different cell types carry different types of toxin receptors, which also means that exosomes secreted by different cells may be able to trap and neutralize different bacterial toxins. } blowing bubbles to kill bacteria (source: see watermark) based on the above research, Cadwell team believes that their research shows that cell secretory exosomes may be a new innate immune response against bacterial infection. it can trap all kinds of toxins released by bacteria by releasing exosomes carrying toxin binding proteins, so as to prevent human cells or tissues from being damaged by bacteria. Torres believes that this research not only gives us a new understanding of mammalian defense against infection, but also proposes a new strategy to strengthen the immune system, which can absorb bacterial toxins by injecting artificial exosomes into the body, or enhance the human body's defense ability by promoting the production of exosomes [4]. singularity cake thinks that science is really fascinating. the audio course "8 lectures on small cell lung cancer" which was built by the singularity cake for 3 months, is coming online. With the 8 lecture course, we can help you review the important exploration and progress in the field of small cell lung cancer in the past 30 years. it only takes 80 minutes to survey the frontier academic progress in the field of small cell lung cancer.