Malaria pigment hemozoin-induced transcriptional remodeling of mouse hematopoietic stem and progenitor cells, granulocyte-macrophage progenitors, and bone marrow monocytes

Trained immunity is the phenomenon whereby innate immune cells such as monocytes or macrophages, and their progenitors in the bone-marrow, undergo functional reprogramming after exposure to certain microbial and danger signals, altering their responses to future exposures. In this study, we performed a non-lethal Plasmodium yoelii 17XNL (Py) infection in wild-type C57/BL6J mice to investigate the underlying mechanism of Py-induced myelopoiesis and performed transcriptomic analysis on HSPCs, GMPs, and monocytes 6 weeks following exposure. Next cecal ligation and puncture (CLP) was used to model sepsis in vivo as a secondary exposure, and the transcriptomes of PBS and Py-exposed monocytes were generated. C57/b6 mice were infected with Plasmodium yoelii for 6 weeks and then infected with CLP or left untreated for additional 3 hours. Mice were then sacrificed and bone marrow were harvested for HSPC, GMP or monoctes isolation. Different cells were sorted by BD Aria III with the following surface markers. HSPCs were sorted from Lin- cKit+ CD34+ population. GMPs were sorted from Lin-Ckit+Sca1-Cd16/32+CD34- population. Monocytes were sorted from CD45+CD11b+Ly6Chi Ly6G- population.