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  • CXCL5-mediated recruitment of neutrophils into the peritoneal cavity of Gdf15-deficient mice protects against abdominal sepsis.

CXCL5-mediated recruitment of neutrophils into the peritoneal cavity of Gdf15-deficient mice protects against abdominal sepsis.

Proceedings of the National Academy of Sciences of the United States of America (2020-05-20)
Isa Santos, Henrique G Colaço, Ana Neves-Costa, Elsa Seixas, Tiago R Velho, Dora Pedroso, André Barros, Rui Martins, Nuno Carvalho, Didier Payen, Sebastian Weis, Hyon-Seung Yi, Minho Shong, Luís F Moita
PMID32424099
ABSTRACT

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.