PUBLICATION
Oxoeicosanoid signaling mediates early antimicrobial defense in zebrafish
- Authors
- Ma, Y., Hui, K.L., Gelashvili, Z., Niethammer, P.
- ID
- ZDB-PUB-230115-1
- Date
- 2023
- Source
- Cell Reports 42: 111974111974 (Journal)
- Registered Authors
- Niethammer, Philipp
- Keywords
- CP: Immunology, CP: Metabolism
- Datasets
- GEO:GSE201604
- MeSH Terms
-
- Animals
- Anti-Infective Agents*
- Arachidonic Acid/metabolism
- Humans
- Mice
- Receptors, G-Protein-Coupled
- Signal Transduction
- Zebrafish*/metabolism
- PubMed
- 36640321 Full text @ Cell Rep.
Citation
Ma, Y., Hui, K.L., Gelashvili, Z., Niethammer, P. (2023) Oxoeicosanoid signaling mediates early antimicrobial defense in zebrafish. Cell Reports. 42:111974111974.
Abstract
5-oxoETE is a bioactive lipid derived from arachidonic acid generated when phospholipase A2 activation coincides with oxidative stress. Through its G protein-coupled receptor OXER1, pure 5-oxoETE is a potent leukocyte chemoattractant. Yet, its physiological function has remained elusive owing to the unusual OXER1 conservation pattern. OXER1 is conserved from fish to primates but not in rodents, precluding genetic loss-of-function studies in mouse. To determine its physiological role, we combine transcriptomic, lipidomic, and intravital imaging assays with genetic perturbations of the OXER1 ortholog hcar1-4 in zebrafish. Pseudomonas aeruginosa infection induces the synthesis of 5-oxoETE and its receptor, along with other inflammatory pathways. Hcar1-4 deletion attenuates neutrophil recruitment and decreases post-infection survival, which could be rescued by ectopic expression of hcar1-4 or human OXER1. By revealing 5-oxoETE as dominant lipid regulator of the early antimicrobial response in a non-rodent vertebrate, our work expands the current, rodent-centric view of early inflammation.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping