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Curr Opin Hematol. 2015 Jul;22(4):293-301. doi: 10.1097/MOH.0000000000000148.

Fight or flight: regulation of emergency hematopoiesis by pyroptosis and necroptosis.

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aDivision of Hematology/Oncology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA bThe Walter and Eliza Hall Institute of Medical Research cDepartment of Medical Biology, University of Melbourne, Parkville, Victoria, Australia dDepartment of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.



A feature of the innate immune response that is conserved across kingdoms is the induction of cell death. In this review, we discuss the direct and indirect effects of increased inflammatory cell death, including pyroptosis - a caspase-1-dependent cell death - and necroptosis - a receptor-interacting protein kinase 3/mixed lineage kinase domain-like protein-dependent, caspase-independent cell death - on emergency hematopoiesis.


Activation of nonapoptotic cell death pathways during infection can trigger release of cytokines and/or damage-associated molecular patterns such as interleukin (IL)-1α, IL-1β, IL-18, IL-33, high-mobility group protein B1, and mitochondrial DNA to promote emergency hematopoiesis. During systemic infection, pyroptosis and necroptosis can directly kill hematopoietic stem and progenitor cells, which results in impaired hematopoiesis, cytopenia, and immunosuppression. Although originally described as discrete entities, there now appear to be more intimate connections between the nonapoptotic and death receptor signaling pathways.


The choice to undergo pyroptotic and necroptotic cell death constitutes a rapid response system serving to eliminate infected cells, including hematopoietic stem and progenitor cells. This system has the potential to be detrimental to emergency hematopoiesis during severe infection. We discuss the potential of pharmacological intervention for the pyroptosis and necroptosis pathways that may be beneficial during periods of infection and emergency hematopoiesis.

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