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

Research output: Contribution to journalArticle

27 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1088-1103
Number of pages16
JournalKidney International
Volume91
Issue number5
DOIs
Publication statusPublished - May 1 2017
Externally publishedYes

Keywords

  • dendritic cell
  • macrophage
  • peritoneal dialysis
  • peritoneal inflammation
  • peritonitis

ASJC Scopus subject areas

  • Nephrology

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  • Cite this

    Liao, C. T., Andrews, R., Wallace, L. E., Khan, M. W. A., Kift-Morgan, A., Topley, N., Fraser, D. J., & Taylor, P. R. (2017). Peritoneal macrophage heterogeneity is associated with different peritoneal dialysis outcomes. Kidney International, 91(5), 1088-1103. https://doi.org/10.1016/j.kint.2016.10.030