CXCL5-mediated recruitment of neutrophils into the peritoneal cavity of Gdf15-deficient mice protects against abdominal sepsis.
Isa SantosHenrique G ColaçoAna Neves CostaElsa SeixasTiago R VelhoDora PedrosoAndré BarrosRui MartinsNuno CarvalhoDidier PayenSebastian WeisHyon Seung YiMinho ShongLuis Ferreira MoitaPublished in: Proceedings of the National Academy of Sciences of the United States of America (2020)
Sepsis is a life-threatening organ dysfunction condition caused by a dysregulated host response to an infection. Here we report that the circulating levels of growth and differentiation factor-15 (GDF15) are strongly increased in septic shock patients and correlate with mortality. In mice, we find that peptidoglycan is a potent ligand that signals through the TLR2-Myd88 axis for the secretion of GDF15, and that Gdf15-deficient mice are protected against abdominal sepsis due to increased chemokine CXC ligand 5 (CXCL5)-mediated recruitment of neutrophils into the peritoneum, leading to better local bacterial control. Our results identify GDF15 as a potential target to improve sepsis treatment. Its inhibition should increase neutrophil recruitment to the site of infection and consequently lead to better pathogen control and clearance.
Keyphrases
- metabolic syndrome
- septic shock
- acute kidney injury
- intensive care unit
- end stage renal disease
- toll like receptor
- newly diagnosed
- ejection fraction
- chronic kidney disease
- oxidative stress
- prognostic factors
- type diabetes
- cardiovascular disease
- risk assessment
- risk factors
- coronary artery disease
- candida albicans
- skeletal muscle
- climate change