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Manipulating niche composition limits damage to haematopoietic stem cells during Plasmodium infection.

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Haltalli, Myriam LR  ORCID logo
Wilson, Nicola K 
Eilers, Kira 
Lipien, Alexander 


Severe infections are a major stress on haematopoiesis, where the consequences for haematopoietic stem cells (HSCs) have only recently started to emerge. HSC function critically depends on the integrity of complex bone marrow (BM) niches; however, what role the BM microenvironment plays in mediating the effects of infection on HSCs remains an open question. Here, using a murine model of malaria and combining single-cell RNA sequencing, mathematical modelling, transplantation assays and intravital microscopy, we show that haematopoiesis is reprogrammed upon infection, whereby the HSC compartment turns over substantially faster than at steady-state and HSC function is drastically affected. Interferon is found to affect both haematopoietic and mesenchymal BM cells and we specifically identify a dramatic loss of osteoblasts and alterations in endothelial cell function. Osteo-active parathyroid hormone treatment abolishes infection-triggered HSC proliferation and-coupled with reactive oxygen species quenching-enables partial rescuing of HSC function.



Animals, Bone Marrow Cells, Endothelial Cells, Gene Expression Profiling, Hematopoiesis, Hematopoietic Stem Cells, Humans, Malaria, Mesenchymal Stem Cells, Mice, Inbred C57BL, Mice, Knockout, Osteoblasts, Parathyroid Hormone, Plasmodium berghei, Reactive Oxygen Species, Stem Cell Niche

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Nat Cell Biol

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Springer Science and Business Media LLC


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Wellcome Trust (206328/Z/17/Z)
Bloodwise (18002)
Wellcome Trust (203151/Z/16/Z)
Cancer Research UK (21762)
Leukaemia & Lymphoma Research (12029)
Medical Research Council (MR/M008975/1)
MRC (1803527)
Royal Society (IEC\R3\193020)
Global Health Innovative Technology Fund (GHIT) (via Kanazawa University) (RFP-TRP-2019-002)
Royal Society (RGS\R1\201293)
Medical Research Council (MC_PC_12009)
Medical Research Council (MR/N00227X/1)
Wellcome Trust, Blood Cancer UK, CRUK, MRC, BBSRC, ERC, Royal Society
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