Epigenitic regular on effect of Hpb-colonized and -trained mice on peritoneal macrophage

Enteric helminth infections shape host immunity to other pathogens. However, it remains uncertain whether helminth infections following deworming treatment could induce long-term alterations in the host immune system. Here, we demonstrate that infection with Hpb, even after anthelmintic-mediated clearance, induces trained immunity to confer long-lasting cross-protection against lethal S. aureus challenge. This protective effect is associated with the prolonged expansion and functional reprogramming of peritoneal macrophages. Mechanistically, we identify the IL-4/IL-4Rα signaling axis, driven by Hpb-induced Th2 skewing, is essential for both peritoneal macrophage accumulation and Cybb-dependent reactive oxygen species (ROS) enrichment. Notably, Th2 cells, rather than eosinophils or basophils, serve as the predominant source of IL-4 and persist in the peritoneal cavity for at least three weeks post Hpb clearance. Collectively, these findings uncover a novel helminth-mediated trained immunity that promotes host resistance to systemic bacterial infection through Th2-dependent reprogramming of peripheral peritoneal macrophage.