PUBLICATION
Heme oxygenase limits Mycobacterium marinum infection-induced detrimental ferrostatin-sensitive cell death in zebrafish
- Authors
- Luo, K., Stocker, R., Britton, W.J., Kikuchi, K., Oehlers, S.H.
- ID
- ZDB-PUB-210922-21
- Date
- 2021
- Source
- The FEBS journal 289(3): 671-681 (Journal)
- Registered Authors
- Oehlers, Stefan
- Keywords
- Hmox1, ferroptosis, granuloma, iron, mycobacteria
- MeSH Terms
-
- Animals
- Cell Death/genetics
- Cyclohexylamines/metabolism
- Disease Models, Animal
- Heme/genetics
- Heme Oxygenase-1/genetics*
- Homeostasis
- Host-Pathogen Interactions/genetics
- Humans
- Iron/metabolism*
- Macrophages/microbiology
- Mycobacterium Infections, Nontuberculous
- Mycobacterium marinum/genetics
- Mycobacterium marinum/pathogenicity
- Mycobacterium tuberculosis/genetics
- Mycobacterium tuberculosis/pathogenicity
- Phenylenediamines/metabolism
- Tuberculosis/genetics*
- Tuberculosis/microbiology
- Zebrafish/genetics
- Zebrafish/microbiology
- Zebrafish Proteins/genetics*
- PubMed
- 34544203 Full text @ FEBS J.
Citation
Luo, K., Stocker, R., Britton, W.J., Kikuchi, K., Oehlers, S.H. (2021) Heme oxygenase limits Mycobacterium marinum infection-induced detrimental ferrostatin-sensitive cell death in zebrafish. The FEBS journal. 289(3):671-681.
Abstract
Iron homeostasis is essential for both sides of the host-pathogen interface. Restricting access of iron slows bacterial growth while iron is also a necessary co-factor for host immunity. Heme oxygenase 1 (HMOX1) is a critical regulator of iron homeostasis that catalyses the liberation of iron during degradation of heme. It is also a stress-responsive protein that can be rapidly upregulated and confers protection to the host. Although a protective role of HMOX1 has been demonstrated in a variety of diseases, the role of HMOX1 in Mycobacterium tuberculosis infection is equivocal across experiments with different host-pathogen combinations. Here, we use the natural host-pathogen pairing of the zebrafish-Mycobacterium marinum infection platform to study the role of zebrafish heme oxygenase in mycobacterial infection. We identify zebrafish Hmox1a as the relevant functional paralog of mammalian HMOX1 and demonstrate a conserved role for Hmox1a in protecting the host from M. marinum infection. Using genetic and chemical tools, we show zebrafish Hmox1a protects the host against M. marinum infection by reducing infection-induced iron accumulation and ferrostatin-sensitive cell death.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping