PUBLICATION
CXCL20a, a Teleost-Specific Chemokine That Orchestrates Direct Bactericidal, Chemotactic, and Phagocytosis-Killing-Promoting Functions, Contributes to Clearance of Bacterial Infections
- Authors
- Zhang, Y., Xiao, X., Hu, Y., Liao, Z., Zhu, W., Jiang, R., Yang, C., Zhang, Y., Su, J.
- ID
- ZDB-PUB-210901-1
- Date
- 2021
- Source
- Journal of immunology (Baltimore, Md. : 1950) 207(7): 1911-1925 (Journal)
- Registered Authors
- Su, Jianguo
- Keywords
- none
- MeSH Terms
-
- Aeromonas hydrophila/physiology*
- Animals
- Bacteriolysis
- Carps/immunology*
- Chemokines, CXC/genetics
- Chemokines, CXC/metabolism*
- Chemotaxis
- Cloning, Molecular
- Cytotoxicity, Immunologic
- Fish Diseases/immunology*
- Fish Proteins/genetics
- Fish Proteins/metabolism*
- Gram-Negative Bacterial Infections/immunology*
- Phagocytosis
- Zebrafish/immunology*
- PubMed
- 34462313 Full text @ J. Immunol.
Citation
Zhang, Y., Xiao, X., Hu, Y., Liao, Z., Zhu, W., Jiang, R., Yang, C., Zhang, Y., Su, J. (2021) CXCL20a, a Teleost-Specific Chemokine That Orchestrates Direct Bactericidal, Chemotactic, and Phagocytosis-Killing-Promoting Functions, Contributes to Clearance of Bacterial Infections. Journal of immunology (Baltimore, Md. : 1950). 207(7):1911-1925.
Abstract
The major role of chemokines is to act as a chemoattractant to guide the migration of immune cells to the infectious sites. In the current study, we found that CiCXCL20a, a teleost-specific chemokine from grass carp (Ctenopharyngodon idella), demonstrates broad-spectrum, potent, direct bactericidal activity and immunomodulatory functions to bacterial infections, apart from the chemotaxis. CiCXCL20a kills bacteria by binding, mainly targeting acid lipids, perforating bacterial membrane, resulting in bacterial cytoplasm leakage and death. CiCXCL20a aggregates and neutralizes LPS, agglutinates Gram-negative bacteria, and binds to peptidoglycan and Gram-positive bacteria, but not agglutinate them. All the complexes may be phagocytized and cleared away. CiCXCL20a chemoattracts leukocytes, facilitates phagocytosis of myeloid leukocytes, not lymphoid leukocytes, and enhances the bacteria-killing ability in leukocytes. We further identified its receptor CiCXCR3.1b1. Furthermore, we investigated the physiological roles of CiCXCL20a against Aeromonas hydrophila infection in vivo. The recombinant CiCXCL20a increases the survival rate and decreases the tissue bacterial loads, edema, and lesions. Then, we verified this function by purified CiCXCL20a Ab blockade, and the survival rate decreases, and the tissue bacterial burdens increase. In addition, zebrafish (Danio rerio) DrCXCL20, an ortholog of CiCXCL20a, was employed to verify the bactericidal function and mechanism. The results indicated that DrCXCL20 also possesses wide-spectrum, direct bactericidal activity through membrane rupture mechanism. The present study, to our knowledge, provides the first evidence that early vertebrate chemokine prevents from bacterial infections by direct bactericidal and phagocytosis-killing-promoting manners. The results also demonstrate the close functional relationship between chemokines and antimicrobial peptides.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping