Differentiation Kinetics of Hematopoietic Stem and Progenitor Cells In Vivo Are Not Affected by β-Glucan Treatment in Trained Immunity

Agonists of trained immunity induce epigenetic changes in hematopoietic stem and progenitor cells (HSPCs) to generate long-lasting immune protection. Although trained HSPCs generate myeloid cells with increased responsiveness to secondary challenges, whether their differentiation kinetics is affected by prior exposure to inducers of trained immunity remains elusive. Here, we used lineage tracing to examine the cell fates of endothelial protein C receptor-positive hematopoietic stem cells (EPCR⁺ HSCs) and fms-like tyrosine kinase 3-positive multipotent progenitor cells (Flt3⁺ MPPs) in β-glucan-induced trained immunity. We found that although β-glucan triggered the expected expansion of myeloid progenitors, the differentiation behaviors of EPCR⁺ HSCs and Flt3⁺ MPPs in multiple cycles of hematopoietic regeneration were hardly affected. Thus, our results rule out changed kinetics in cell differentiation by EPCR⁺ HSC and Flt3⁺ MPP as the cause of enhanced myelopoiesis upon secondary immune challenges.