PUBLICATION
Infection-experienced HSPCs protect against infections by generating neutrophils with enhanced mitochondrial bactericidal activity
- Authors
- Darroch, H., Keerthisinghe, P., Sung, Y.J., Rolland, L., Prankerd-Gough, A., Crosier, P.S., Astin, J.W., Hall, C.J.
- ID
- ZDB-PUB-230907-53
- Date
- 2023
- Source
- Science advances 9: eadf9904eadf9904 (Journal)
- Registered Authors
- Astin, Jonathan, Crosier, Phil, Darroch, Hannah, Hall, Chris, Keerthisinghe, Pramuk, Rolland, Leah, Sung, Yih Jian
- Keywords
- none
- Datasets
- GEO:GSE217064
- MeSH Terms
-
- Animals
- Anti-Bacterial Agents
- Gene Expression Profiling
- Mitochondria
- Neutrophils*
- Zebrafish*
- PubMed
- 37672586 Full text @ Sci Adv
Citation
Darroch, H., Keerthisinghe, P., Sung, Y.J., Rolland, L., Prankerd-Gough, A., Crosier, P.S., Astin, J.W., Hall, C.J. (2023) Infection-experienced HSPCs protect against infections by generating neutrophils with enhanced mitochondrial bactericidal activity. Science advances. 9:eadf9904eadf9904.
Abstract
Hematopoietic stem and progenitor cells (HSPCs) respond to infection by proliferating and generating in-demand neutrophils through a process called emergency granulopoiesis (EG). Recently, infection-induced changes in HSPCs have also been shown to underpin the longevity of trained immunity, where they generate innate immune cells with enhanced responses to subsequent microbial threats. Using larval zebrafish to live image neutrophils and HSPCs, we show that infection-experienced HSPCs generate neutrophils with enhanced bactericidal functions. Transcriptomic analysis of EG neutrophils uncovered a previously unknown function for mitochondrial reactive oxygen species in elevating neutrophil bactericidal activity. We also reveal that driving expression of zebrafish C/EBPβ within infection-naïve HSPCs is sufficient to generate neutrophils with similarly enhanced bactericidal capacity. Our work suggests that this demand-adapted source of neutrophils contributes to trained immunity by providing enhanced protection toward subsequent infections. Manipulating demand-driven granulopoiesis may provide a therapeutic strategy to boost neutrophil function and treat infectious disease.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping