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

Proc Natl Acad Sci U S A. 2020 Jun 2;117(22):12281-12287. doi: 10.1073/pnas.1918508117. Epub 2020 May 18.

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.

Keywords: CXCL5; GDF15; neutrophils; sepsis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacteremia / genetics
  • Bacteremia / immunology*
  • Bacteremia / microbiology
  • Bacteremia / prevention & control
  • Chemokine CXCL5 / genetics
  • Chemokine CXCL5 / immunology*
  • Female
  • Growth Differentiation Factor 15 / genetics
  • Growth Differentiation Factor 15 / immunology*
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neutrophil Infiltration
  • Neutrophils / immunology*
  • Peritoneal Cavity / microbiology

Substances

  • Chemokine CXCL5
  • Cxcl5 protein, mouse
  • Growth Differentiation Factor 15