PUBLICATION
Tissue-resident trained immunity in hepatocytes protects against septic liver injury in zebrafish
- Authors
- Wang, Z., Liu, Y., Hu, J., You, X., Yang, J., Zhang, Y., Liu, Q., Yang, D.
- ID
- ZDB-PUB-240609-10
- Date
- 2024
- Source
- Cell Reports 43: 114324114324 (Journal)
- Registered Authors
- Yang, Dahai
- Keywords
- CP: Immunology, H3K4me3, hepatocytes, mitophagy, pyroptosis, septic-liver injury, trained immunity, zebrafish, β-glucan
- MeSH Terms
-
- Animals
- Hepatocytes*/immunology
- Hepatocytes*/metabolism
- Histones/metabolism
- Immunity, Innate
- Lectins, C-Type/metabolism
- Lipopolysaccharides
- Liver/immunology
- Liver/metabolism
- Liver/pathology
- Mitophagy
- Pyroptosis*
- Sepsis*/immunology
- Trained Immunity
- Zebrafish*
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- beta-Glucans/pharmacology
- PubMed
- 38850536 Full text @ Cell Rep.
Citation
Wang, Z., Liu, Y., Hu, J., You, X., Yang, J., Zhang, Y., Liu, Q., Yang, D. (2024) Tissue-resident trained immunity in hepatocytes protects against septic liver injury in zebrafish. Cell Reports. 43:114324114324.
Abstract
Trained immunity is classically characterized by long-term functional reprogramming of innate immune cells to combat infectious diseases. Infection-induced organ injury is a common clinical severity phenotype of sepsis. However, whether the induction of trained immunity plays a role in protecting septic organ injury remains largely unknown. Here, through establishing an in vivo β-glucan training and lipopolysaccharide (LPS) challenge model in zebrafish larvae, we observe that induction of trained immunity could inhibit pyroptosis of hepatocytes to alleviate septic liver injury, with an elevated trimethyl-histone H3 lysine 4 (H3K4me3) modification that targets mitophagy-related genes. Moreover, we identify a C-type lectin domain receptor in zebrafish, named DrDectin-1, which is revealed as the orchestrator in gating H3K4me3 rewiring-mediated mitophagy activation and alleviating pyroptosis-engaged septic liver injury in vivo. Taken together, our results uncover tissue-resident trained immunity in maintaining liver homeostasis at the whole-animal level and offer an in vivo model to efficiently integrate trained immunity for immunotherapies.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping