A neutrophil–B-cell axis impacts tissue damage control in a mouse model of intraabdominal bacterial infection via Cxcr4

• DOI: 10.7554/elife.78291
• Publication Date: 2022-09-30T16:01:26Z
• Authors: Riem Gawish; Barbara Maier; Georg Obermayer; Martin L Watzenboeck; Anna-Dorothea Gorki; Federica Quattrone; Asma Farhat; Karin Lakovits; Anastasiya Hladik; Ana Korosec; Arman Alimohammadi; Ildiko Mesteri; Felicitas Oberndo...; Fiona Oakley; John Brain; Louis Boon; Irene Lang; Christoph J Binder; Sylvia Knapp
• Keywords: Neutrophil Extracellular Traps

Sepsis is a life-threatening condition characterized by uncontrolled systemic inflammation and coagulation, leading to multiorgan failure. Therapeutic options prevent sepsis-associated immunopathology remain scarce. Here, we established mouse model of long-lasting disease tolerance during severe sepsis, manifested diminished immunothrombosis organ damage in spite high pathogen burden. We found that both neutrophils B cells emerged as key regulators tissue integrity. Enduring changes the transcriptional profile include upregulated Cxcr4 expression protected, tolerant hosts. Neutrophil upregulation required presence cells, suggesting promoted improving control via suppression neutrophils' tissue-damaging properties. Finally, therapeutic administration agonist successfully prevented liver sepsis. Our findings highlight importance critical B-cell/neutrophil interaction sepsis establish neutrophil activation potential means promote