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Peritoneal macrophage heterogeneity is associated with different peritoneal dialysis outcomes

Liao, Chia-Te, Andrews, Robert, Wallace, Leah, Khan, Mohd, Kift-Morgan, Ann, Topley, Nicholas, Fraser, Donald and Taylor, Philip Rosser 2017. Peritoneal macrophage heterogeneity is associated with different peritoneal dialysis outcomes. Kidney International 91 (5) , pp. 1088-1103. 10.1016/j.kint.2016.10.030

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Abstract

Peritonitis remains the major obstacle for the maintenance of long-term peritoneal dialysis and dysregulated host peritoneal immune responses may compromise local anti-infectious defense, leading to treatment failure. Whilst, tissue mononuclear phagocytes, comprising macrophages and dendritic cells, are central to a host response to pathogens and the development of adaptive immune responses, they are poorly characterized in the human peritoneum. Combining flow cytometry with global transcriptome analysis, the phenotypic features and lineage identity of the major CD14+ macrophage and CD1c+ dendritic cell subsets in dialysis effluent were defined. Their functional specialization was reflected in cytokine generation, phagocytosis, and antigen processing/presentation. By analyzing acute bacterial peritonitis, stable (infection-free) and new-starter patients receiving peritoneal dialysis, we identified a skewed distribution of macrophage to dendritic cell subsets (increasing ratio) that associated with adverse peritonitis outcomes, history of multiple peritonitis episodes, and early catheter failure, respectively. Intriguingly, we also noted significant alterations of macrophage heterogeneity, indicative of different maturation and activation states that were associated with different peritoneal dialysis outcomes. Thus, our studies delineate peritoneal dendritic cells from macrophages within dialysate, and define cellular characteristics associated with peritoneal dialysis treatment failure. These are the first steps to unravelling the detrimental adaptive immune responses occurring as a consequence of peritonitis.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Systems Immunity Research Institute (SIURI)
Publisher: Elsevier
ISSN: 0085-2538
Funders: MRC, Wellcome Trust, Marie Curie Fellowship, NISCHR
Date of First Compliant Deposit: 12 December 2016
Date of Acceptance: 20 October 2016
Last Modified: 26 Dec 2018 21:57
URI: http://orca.cf.ac.uk/id/eprint/96716

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