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Neutrophil-derived miR-223 as local biomarker of bacterial peritonitis

Brook, Amy C., Jenkins, Robert H., Clayton, Aled, Kift-Morgan, Ann, Raby, Anne-Catherine, Shephard, Alex P., Mariotti, Barbara, Cuff, Simone M., Bazzoni, Flavia, Bowen, Timothy, Fraser, Donald J. and Eberl, Matthias 2019. Neutrophil-derived miR-223 as local biomarker of bacterial peritonitis. Scientific Reports 9 , 10136. 10.1038/s41598-019-46585-y

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Abstract

Infection remains a major cause of morbidity, mortality and technique failure in patients with end stage kidney failure who receive peritoneal dialysis (PD). Recent research suggests that the early inflammatory response at the site of infection carries diagnostically relevant information, suggesting that organ and pathogen-specific “immune fingerprints” may guide targeted treatment decisions and allow patient stratification and risk prediction at the point of care. Here, we recorded microRNA profiles in the PD effluent of patients presenting with symptoms of acute peritonitis and show that elevated peritoneal miR-223 and reduced miR-31 levels were useful predictors of bacterial infection. Cell culture experiments indicated that miR-223 was predominantly produced by infiltrating immune cells (neutrophils, monocytes), while miR-31 was mainly derived from the local tissue (mesothelial cells, fibroblasts). miR-223 was found to be functionally stabilised in PD effluent from peritonitis patients, with a proportion likely to be incorporated into neutrophil-derived exosomes. Our study demonstrates that microRNAs are useful biomarkers of bacterial infection in PD-related peritonitis and have the potential to contribute to disease-specific immune fingerprints. Exosome-encapsulated microRNAs may have a functional role in intercellular communication between immune cells responding to the infection and the local tissue, to help clear the infection, resolve the inflammation and restore homeostasis.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Advanced Research Computing @ Cardiff (ARCCA)
Medicine
Additional Information: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
Publisher: Nature Publishing Group
ISSN: 2045-2322
Funders: Medical Research Council
Date of First Compliant Deposit: 15 July 2019
Date of Acceptance: 1 July 2019
Last Modified: 18 Jan 2021 14:00
URI: http://orca.cardiff.ac.uk/id/eprint/124183

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