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Lookup NU author(s): Dr Riem Gawish, Professor Fiona OakleyORCiD, Dr John Brain
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2022, eLife Sciences Publications Ltd. All rights reserved. Sepsis is a life-threatening condition characterized by uncontrolled systemic inflammation and coagulation, leading to multiorgan failure. Therapeutic options to prevent sepsis-associated immunopathology remain scarce. Here, we established a mouse model of long-lasting disease tolerance during severe sepsis, manifested by diminished immunothrombosis and organ damage in spite of a high pathogen burden. We found that both neutrophils and B cells emerged as key regulators of tissue integrity. Enduring changes in the transcriptional profile of neutrophils include upregulated Cxcr4 expression in protected, tolerant hosts. Neutrophil Cxcr4 upregulation required the presence of B cells, suggesting that B cells promoted disease tolerance by improving tissue damage control via the suppression of neutrophils’ tissue-damaging properties. Finally, therapeutic administration of a Cxcr4 agonist successfully promoted tissue damage control and prevented liver damage during sepsis. Our findings highlight the importance of a critical B-cell/neutrophil interaction during sepsis and establish neutrophil Cxcr4 activation as a potential means to promote disease tolerance during sepsis.
Author(s): Gawish R, Maier B, Obermayer G, Watzenboeck ML, Gorki A-D, Quattrone F, Farhat A, Lakovits K, Hladik A, Korosec A, Alimohammadi A, Mesteri I, Oberndorfer F, Oakley F, Brain J, Boon L, Lang I, Binder CJ, Knapp S
Publication type: Article
Publication status: Published
Journal: eLife
Year: 2022
Volume: 11
Online publication date: 30/09/2022
Acceptance date: 16/09/2022
Date deposited: 25/10/2022
ISSN (electronic): 2050-084X
Publisher: eLife Sciences Publications Ltd
URL: https://doi.org/10.7554/eLife.78291
DOI: 10.7554/eLife.78291
PubMed id: 36178806
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