Neutrophils mediate Salmonella Typhimurium clearance through the GBP4 inflammasome-dependent production of prostaglandins
- Tyrkalska, S.D., Candel, S., Angosto, D., Gómez-Abellán, V., Martín-Sánchez, F., García-Moreno, D., Zapata-Pérez, R., Sánchez-Ferrer, Á., Sepulcre, M.P., Pelegrín, P., Mulero, V.
- Nature communications 7: 12077 (Journal)
- Registered Authors
- Mulero, Victor
- Bacterial infection, Inflammasome, Medical research, Neutrophils
- MeSH Terms
- Caspase Activation and Recruitment Domain
- GTP-Binding Proteins/immunology*
- Leukotriene B4/immunology
- Organisms, Genetically Modified
- Prostaglandin D2/biosynthesis*
- Salmonella typhimurium
- 27363812 Full text @ Nat. Commun.
Tyrkalska, S.D., Candel, S., Angosto, D., Gómez-Abellán, V., Martín-Sánchez, F., García-Moreno, D., Zapata-Pérez, R., Sánchez-Ferrer, Á., Sepulcre, M.P., Pelegrín, P., Mulero, V. (2016) Neutrophils mediate Salmonella Typhimurium clearance through the GBP4 inflammasome-dependent production of prostaglandins. Nature communications. 7:12077.
Inflammasomes are cytosolic molecular platforms that alert the immune system about the presence of infection. Here we report that zebrafish guanylate-binding protein 4 (Gbp4), an IFNγ-inducible GTPase protein harbouring a C-terminal CARD domain, is required for the inflammasome-dependent clearance of Salmonella Typhimurium (ST) by neutrophils in vivo. Despite the presence of the CARD domain, Gbp4 requires the universal inflammasome adaptor Asc for mediating its antibacterial function. In addition, the GTPase activity of Gbp4 is indispensable for inflammasome activation and ST clearance. Mechanistically, neutrophils are recruited to the infection site through the inflammasome-independent production of the chemokine (CXC motif) ligand 8 and leukotriene B4, and then mediate bacterial clearance through the Gbp4 inflammasome-dependent biosynthesis of prostaglandin D2. Our results point to GBPs as key inflammasome adaptors required for prostaglandin biosynthesis and bacterial clearance by neutrophils and suggest that transient activation of the inflammasome may be used to treat bacterial infections.
Genes / Markers
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes