Mechanism of innate immune memory induced by bacterial-derived exopolysaccharide 4414

Abstract Description Inflammatory diseases are a rising burden in contemporary society. Solutions for some of these inflammatory responses may be obtained from a deeper understanding of mechanisms underlying trained tolerance, or memory of the innate immune system. Trained tolerance is a phenomenon in which primed innate cells respond without inflammation upon encounter with a secondary challenge. We identified an exopolysaccharide (EPS) molecule from the bacterium Bacillus subtilis, that prevents inflammation in mice later exposed to LPS. This EPS tolerance also protects mice from C. rodentium- induced colitis, sepsis caused by infection with Staphylococcus aureus, and allergic eosinophilia. Here, we show that EPS protects mice from LPS-induced inflammation and this protection starts 16 hrs after injection of EPS and lasts for at least a week. The long time of EPS protection could be explained by EPS affecting both peripheral myeloid cells as well as bone marrow progenitor cells. Within a day after administering EPS, a novel group of IL-27-producing myeloid cells appears in peritoneum and at the same time expansion of hematopoietic stem cells and myeloid progenitors occurs in the bone marrow. We hypothesize that IL-27-producing peritoneal cells provide the effector inhibition of the LPS inflammatory response, and that IL-27 from these effector cells drives the expansion of hematopoietic and myelopoietic progenitor cells in BM that are responsible for maintaining long-term central innate memory. Funding Sources None Topic Categories Immune Response Regulation: Cellular Mechanisms (IRC)