The role of innate memory in Helicobacter pylori infection

Helicobacter pylori (H. pylori) is a cunning stomach bacterium that infects half of the world`s population and is considered the main cause of stomach cancer. While the immune system typically mounts a strong defense against invading pathogens, H. pylori has developed the remarkable ability to evade this defense and promote a chronic inflammatory response. The precise mechanisms of these processes have remained largely unknown and are now the focus of intensive research. Our preliminary data has revealed a remarkable phenomenon: cells of the innate immune system react hypersensitively to bacterial cell components within 24 hours of an H. pylori infection, but surprisingly lose this hypersensitivity after a six-day break. We therefore hypothesize that H. pylori induces unique innate memory responses, leading to chronic inflammation on one hand while suppressing protective T-cell responses, thereby favoring the survival of the dangerous stomach pathogen. To better understand these exciting discoveries, we are employing state-of-the-art cellular models, including co-cultures of "Mini-Stomach" organoids and immune cells, as well as short- term and long-term infection models. Advanced analysis methods such as ChIP-seq, ATAC- seq, and comparative proteomics are being used to decipher the molecular mechanisms and epigenetic changes behind innate memory effects. The role of outer membrane vesicles (OMVs) from H. pylori and various mutant strains is also under intense investigation. This innovative project suggests that previously unexplored innate memory responses could be the basis for H. pylori-induced chronic inflammation and the immune system`s inability to eliminate the pathogen. A series of advanced experiments, including exploring a potential connection between OMVs and innate memory responses, are being conducted. The creation of 3D "Mini-Stomach"/immune cell co-cultures is another innovative aspect in H. pylori research, effectively replicating complex cell interactions under physiological conditions. This groundbreaking research not only promises a deeper understanding of H. pylori infection but also potential approaches for developing new therapies against stomach cancer.