PUBLICATION
Neutralization of mitochondrial superoxide by superoxide dismutase 2 promotes bacterial clearance and regulates phagocyte numbers in zebrafish
- Authors
- Peterman, E.M., Sullivan, C., Goody, M.F., Rodriguez-Nunez, I., Yoder, J.A., Kim, C.H.
- ID
- ZDB-PUB-141112-3
- Date
- 2015
- Source
- Infection and Immunity 83(1): 430-40 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Animals
- Immunity, Innate*
- Leukocyte Count
- Macrophages/enzymology
- Macrophages/immunology*
- Mitochondria/enzymology*
- Mitochondria/metabolism*
- Pseudomonas aeruginosa/immunology*
- Superoxide Dismutase/metabolism*
- Superoxides/metabolism*
- Zebrafish
- PubMed
- 25385799 Full text @ Infect. Immun.
Citation
Peterman, E.M., Sullivan, C., Goody, M.F., Rodriguez-Nunez, I., Yoder, J.A., Kim, C.H. (2015) Neutralization of mitochondrial superoxide by superoxide dismutase 2 promotes bacterial clearance and regulates phagocyte numbers in zebrafish. Infection and Immunity. 83(1):430-40.
Abstract
Mitochondria are primarily known as the location for the electron transport chain and energy production in cells. More recently, mitochondria have been shown to be signaling centers for apoptosis and inflammation. Reactive oxygen species (ROS) generated as byproducts of the electron transport chain within mitochondria significantly impact cellular signaling pathways. Due to the toxic nature of ROS, mitochondria possess an antioxidant enzyme, superoxide dismutase 2 (SOD2), to neutralize ROS. If mitochondrial antioxidant enzymes are overwhelmed during severe infections, mitochondrial dysfunction can occur and lead to multi-organ failure or death. Pseudomonas aeruginosa is an opportunistic pathogen that can infect immunocompromised patients. Infochemicals and exotoxins associated with P. aeruginosa are capable of causing mitochondrial dysfunction. In this work, we describe the roles of SOD2 and mitochondrial ROS regulation in the zebrafish innate immune response to Pseudomonas aeruginosa infection. Sod2 is upregulated in mammalian macrophages and neutrophils in response to LPS in vitro, and sod2 knockdown in zebrafish results in increased bacterial burden. Further investigation revealed that phagocyte numbers are compromised in Sod2-deficient zebrafish. Addition of the mitochondrial-targeted ROS scavenging chemical MitoTEMPO rescues neutrophil numbers and reduces the bacterial burden in Sod2-deficient zebrafish. Our work highlights the importance of mitochondrial ROS regulation by SOD2 in the context of innate immunity and supports the use of mitochondrial-targeted ROS scavengers as potential adjuvant therapies during severe infections.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping