Bone marrow (BM) transfer from flagellin-treated mice has been reported to improve the survival of lethally-irradiated mice. Although the mechanism for flagellin’s antiviral and antibacterial effects have been elucidated, there remains a gap in knowledge regarding its radioprotective effects.

Here, we report that flagellin treatment results in a 5-fold increase in the proliferation of Lin^-Sca-1⁺C-Kit⁺(LSK) cells, a heterogeneous stem and multipotent cell population in BM, with the most striking increase within the ST-HSC, MPP2 and MPP3 subpopulations. Furthermore, the presence of TLR5 but not NLRC4 on radiosensitive, non-LSK cells in BM was both sufficient and necessary for the observed phenomenon. Finally, adoptive transfer of MPP3 cells along with an insufficient amount of whole bone marrow cells (WBM) to lethally-irradiated mice significantly improved their survival, recapitulating the effects of Whole bone marrow from flagellin-treated mice.