PUBLICATION

Dysregulated hemolysin promotes bacterial outer membrane vesicles-induced pyroptotic-like cell death in zebrafish

Authors
Wen, Y., Chen, S., Jiang, Z., Wang, Z., Tan, J., Hu, T., Wang, Q., Zhou, X., Zhang, Y., Liu, Q., Yang, D.
ID
ZDB-PUB-190201-7
Date
2019
Source
Cellular Microbiology   21(6): e13010 (Journal)
Registered Authors
Keywords
Edwardsiella piscicida, bacterial outer membrane vesicles, hemolysin, pyroptotic-like cell death, zebrafish intestinal infection
MeSH Terms
  • Endocytosis
  • Animals
  • Dynamins/antagonists & inhibitors
  • Dynamins/metabolism
  • Intestines/immunology
  • Intestines/microbiology
  • Inflammasomes/immunology*
  • Inflammasomes/metabolism
  • Bacterial Outer Membrane/immunology
  • Bacterial Outer Membrane/metabolism*
  • Inflammation/immunology
  • Larva/immunology
  • Larva/microbiology
  • Pyroptosis*
  • Edwardsiella/metabolism*
  • Edwardsiella/pathogenicity
  • Zebrafish/immunology*
  • Zebrafish/microbiology
  • Immunity, Innate
  • Hemolysin Proteins/genetics
  • Hemolysin Proteins/immunology*
  • Hemolysin Proteins/metabolism
  • Caspases/metabolism
PubMed
30701651 Full text @ Cell. Microbiol.
Abstract
Inflammasomes are important innate immune components in mammals. However, the bacterial factors modulating inflammasome activation in fish, and the mechanisms by which they alter fish immune defenses, remain to be investigated. In this work, a mutant of the fish pathogen Edwardsiella piscicida (E. piscicida), called 0909I, was shown to overexpress hemolysin, which could induce a robust pyroptotic-like cell death dependent on caspase-5-like-activity during infection in fish non-phagocyte cells. E. piscicida hemolysin was found to mainly associate with bacterial outer membrane vesicles (OMVs), which were internalized into the fish cells via a dynamin-dependent endocytosis and induced pyroptotic-like cell death. Importantly, bacterial immersion infection of both larvae and adult zebrafish suggested that dysregulated expression of hemolysin alerts the innate immune system and induces intestinal inflammation to restrict bacterial colonization in vivo. Taken together, these results suggest a critical role of zebrafish innate immunity in monitoring invaded pathogens via detecting the bacterial hemolysin-associated outer membrane vesicles and initiating pyroptotic-like cell death. These new additions to the understanding of hemolysin-mediated pathogenesis in vivo provide evidence for the existence of non-canonical inflammasome signaling in lower vertebrates.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping