CXCL5-mediated recruitment of neutrophils into the peritoneal cavity of Gdf15 -deficient mice protects against abdominal sepsis
| العنوان: | CXCL5-mediated recruitment of neutrophils into the peritoneal cavity of Gdf15 -deficient mice protects against abdominal sepsis |
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| المؤلفون: | André Barros, Tiago R. Velho, Sebastian Weis, Luis F. Moita, Hyon-Seung Yi, Isa Santos, Dora Pedroso, Minho Shong, Henrique G. Colaço, Nuno Borges Carvalho, Rui Martins, Ana Neves-Costa, Didier Payen, Elsa Seixas |
| المصدر: | Proceedings of the National Academy of Sciences of the United States of America Proc Natl Acad Sci U S A BioRxiv Proceedings of the National Academy of Sciences bioRxiv |
| بيانات النشر: | Proceedings of the National Academy of Sciences, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Male, Chemokine CXCL5, Chemokine, Growth Differentiation Factor 15, Neutrophils, Bacteremia, sepsis, Sepsis, Mice, 03 medical and health sciences, Peritoneal cavity, Immunology and Inflammation, 0302 clinical medicine, Peritoneum, medicine, Animals, Humans, Secretion, Peritoneal Cavity, 030304 developmental biology, Mice, Knockout, 0303 health sciences, Multidisciplinary, biology, business.industry, Septic shock, Organ dysfunction, CXCL5, Biological Sciences, medicine.disease, 3. Good health, Mice, Inbred C57BL, GDF15, medicine.anatomical_structure, Neutrophil Infiltration, 030220 oncology & carcinogenesis, Immunology, biology.protein, Female, medicine.symptom, business |
| الوصف: | Significance Sepsis remains a leading cause of death. New insights into its pathophysiology are likely to be key to the development of effective therapeutic strategies against sepsis. Given the role of GDF15 in metabolism regulation and in cachexia during late stages of cancer, features that also occur in sepsis, elucidation of the possible mechanistic role of GDF15 in sepsis is of great importance. We find that septic patients have very high levels of GDF15 in the peripheral blood, which correlate with clinical outcomes. Using Gdf15-deficient mice, we show that GDF15 plays a causal role in sepsis by delaying the local control of infection. These findings suggest GDF15 as a potential therapeutic target in sepsis secondary to a bacterial infection. 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. |
| تدمد: | 1091-6490 0027-8424 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ce589475ad6a49e5f326c019dab85e94Test https://doi.org/10.1073/pnas.1918508117Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....ce589475ad6a49e5f326c019dab85e94 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10916490 00278424 |
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