In the long-term battle between humans and pathogens, an immune factor called "human gut defense factor 5 (HD5)" has a "dual identity" - it can kill bacteria and protect the intestines, as well as help pathogens invade in certain situations. On February 17th, the reporter learned from Xi'an Jiaotong University that the joint research results of the university, France's Pasteur Institute, and Fudan University have revealed for the first time the molecular mechanism behind this contradictory phenomenon, providing new ideas for anti infection treatment. The relevant research results were recently published in the international academic journal Nature Microbiology. HD5 is an antimicrobial peptide secreted by small intestinal cells and has long been considered the "guardian" of the immune system, capable of killing various pathogens. However, Professor Xu Dan from the School of Life Sciences and Technology at Xi'an Jiaotong University and Professor Lu Wuyuan from the School of Basic Medicine at Fudan University found that HD5 would "turn its back" and become an "accomplice" to the invasion of Shigella, which causes bacterial dysentery, into the human body. This discovery overturns traditional cognition and has attracted widespread attention from the scientific community. A multinational research team led by Xi'an Jiaotong University has used multi omics techniques to uncover key clues in the complex molecular maze of host pathogen interactions, uncovering the mystery of HD5's "dual identity". Research has found that HD5 can bind to the P2Y11 receptor on the surface of colon epithelial cells, activate intracellular signaling pathways, and cause drastic changes in the cytoskeleton. Under the microscope, a large number of filamentous pseudopodia will protrude from the surface of cells, which will be utilized by Shigella as a "shortcut" for its invasion. The research team also found that using the P2Y11 receptor specific inhibitor NF157 can effectively block the "betrayal" behavior of HD5 and significantly reduce the infection rate of Shigella. This discovery provides an important target for the development of new anti infective drugs. Regarding this, Xu Dan metaphorically said, "It's like cracking the enemy's communication password, and we can finally accurately cut off the invasion signal of pathogens." Currently, a research team at Xi'an Jiaotong University is developing new anti Shigella drugs based on this discovery and exploring their potential applications in other intestinal infectious diseases. Lu Wuyuan stated that this study not only opens up new directions for anti infective therapy, but also demonstrates the need for future medicine to examine the complex relationships between hosts, pathogens, and the environment from a more systematic perspective. (New Society)