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

Santos, I.; Colaco, H. G.; Neves-Costa, A.; Seixas, E.; Velho, T. R.; Pedroso, D.; Barros, A.; Martins, R.; Weiss, S.; Payen, D.; Yi, H.-S.; Shong, M.; Moita, L. F.

doi:10.1101/613901

bioRxiv · 10.1101/613901

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

Santos, I.·Colaco, H. G.·Neves-Costa, A.·Seixas, E.·Velho, T. R.·Pedroso, D.·Barros, A.·Martins, R.·Weiss, S.·Payen, D.·Yi, H.-S.·Shong, M.·Moita, L. F.

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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-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 animals 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.

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Santos, I., Colaco, H. G., Neves-Costa, A., Seixas, E., Velho, T. R., Pedroso, D., Barros, A., Martins, R., Weiss, S., Payen, D., Yi, H.-S., Shong, M., Moita, L. F.. 2019-04-19. CXCL5-mediated recruitment of neutrophils into the peritoneal cavity of Gdf15-deficient mice protects against abdominal sepsis. https://doi.org/10.1101/613901

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