Peritoneal macrophage heterogeneity is associated with different peritoneal dialysis outcomes

Chia Te Liao, Robert Andrews, Leah E. Wallace, Mohd Wajid A. Khan, Ann Kift-Morgan, Nicholas Topley, Donald J. Fraser, Philip R. Taylor

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33 引文 斯高帕斯(Scopus)

摘要

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.

原文英語
頁(從 - 到)1088-1103
頁數16
期刊Kidney International
91
發行號5
DOIs
出版狀態已發佈 - 五月 1 2017
對外發佈

ASJC Scopus subject areas

  • 腎臟病學

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