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

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.

Exosome-based immunotherapy: a promising approach for cancer treatment

“…Proteomic and RNA microarray analyses indicate that neutrophil-derived exosomes contain proteins, mRNA and miRNAs, which are associated with inflammatory reactions, immune response and cell communication [134][135][136]. Functional studies further discover that neutrophil-derived exosomes can affect the activity of other immune cells, such as macrophages, by transferring several proinflammatory factors [137].…”

Molecular Mechanisms of Action of Emodin: As an Anti-Cardiovascular Disease Drug

“…Studies have reported that MicroRNA (miR)-223 can be invoked as a new potential target for the diagnosis and treatment of inflammatory diseases, such as thrombophlebitis ( Li H. et al., 2020 ), acute peritonitis ( Brook et al., 2019 ), viral myocarditis ( Gou et al., 2018 ), and acute lung injury ( Feng et al., 2017 ). It can inhibit the inflammatory response and prevent the indirect damage in the process of infection ( Yuan et al., 2018 ; Cavallari et al., 2019 ; Kim et al., 2019 ).…”

Development of acoustically isolated extracellular plasma vesicles for biomarker discovery in allogeneic hematopoietic stem cell transplantation

“…This motivated us to further investigate if plasma EV miRNA profiles correlated to transplantation-related complication. We identified miRNAs that positively correlated to infection and, interestingly, all of the top five have been previously reported to play a role in regulating inflammatory processes in different disease settings [ 30 – 34 ]. miR-21 expression was shown to be induced by inflammatory stimuli [ 35 ] and its expression is correlated with C-reactive protein and fibrinogen levels [ 36 ], which indicates that EV miR-21 is worth to be further investigated as potential biomarker for infection/inflammation.…”