Bletilla striata polysaccharide-mediated trained immunity drives the hematopoietic progenitors' expansion and myelopoiesis.

Trained immunity represents a functional state of the innate immune response, characterized by enduring epigenetic reprogramming of innate immune cells. This phenomenon facilitates a sustained and advantageous reaction of myeloid cells to subsequent challenges. Bletilla striata polysaccharide (BSP) is the primary active component of Bletilla striata, mainly consisting of mannose and glucose in its chemical structure. Previous studies have demonstrated BSP's immunomodulatory properties, highlighting its effectiveness in enhancing the immune response. In the present study, we demonstrated that BSP administration induced the trained innate immunity, as evidenced by the BSP-induced generation of mature myeloid cells, especially neutrophils in the peripheral circulation in amouse model of chemotherapy-induced myelosuppression. Furthermore, we showed that BSP-induced trained immunity acts at the level of hematopoietic stem and progenitor cells (HSPCs) and induces the expansion of HSPCs. Mechanistically, our study demonstrated that BSP induced the activation of Notch signaling in HSPCs, and Notch signaling is indispensable for the BSP-mediated generation of trained HSPCs. Collectively, our data demonstrated for the first time that BSP induced trained immunity by regulating theexpansion of the myeloid progenitors. Harnessing trained immunity could be a promising strategy for protection from chemotherapy-induced myelosuppression.