title: Peritoneal macrophage heterogeneity is associated with different peritoneal dialysis outcomes.
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.
authors.affiliation: Systems Immunity University Research Institute and Division of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff, UK.
authors.forename: Chia-Te
authors.initials: CT
authors.lastname: Liao
authors.affiliation: Systems Immunity University Research Institute and Division of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: Andrews
authors.affiliation: Systems Immunity University Research Institute and Division of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff, UK.
authors.forename: Leah E
authors.initials: LE
authors.lastname: Wallace
authors.affiliation: Systems Immunity University Research Institute and Division of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff, UK.
authors.forename: Mohd Wajid A
authors.initials: MW
authors.lastname: Khan
authors.affiliation: Systems Immunity University Research Institute and Division of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff, UK.
authors.forename: Ann
authors.initials: A
authors.lastname: Kift-Morgan
authors.affiliation: Wales Kidney Research Unit, Cardiff University School of Medicine, Heath Park, Cardiff, UK.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Topley
authors.affiliation: Systems Immunity University Research Institute and Division of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff, UK; Wales Kidney Research Unit, Cardiff University School of Medicine, Heath Park, Cardiff, UK.
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Fraser
authors.affiliation: Systems Immunity University Research Institute and Division of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff, UK. Electronic address: TaylorPR@cf.ac.uk.
authors.forename: Philip R
authors.initials: PR
authors.lastname: Taylor
mesh_terms: D056704:Adaptive Immunity; D018949:Antigens, CD1 / Q000378:metabolism; D001424:Bacterial Infections / Q000276:immunology* / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D015314:Dialysis Solutions; D005434:Flow Cytometry; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010530:Peritoneal Dialysis / Q000009:adverse effects*; D010531:Peritoneal Dialysis, Continuous Ambulatory; D010537:Peritoneum / Q000166:cytology; D010538:Peritonitis / Q000276:immunology* / Q000378:metabolism; D059467:Transcriptome
chemical_list: D018949:Antigens, CD1; C437944:CD1C protein, human; D016207:Cytokines; D015314:Dialysis Solutions; D006023:Glycoproteins; D018950:Lipopolysaccharide Receptors
keywords: dendritic cell; macrophage; peritoneal dialysis; peritoneal inflammation; peritonitis