title: Characterization of human peritoneal dendritic cell precursors and their involvement in peritonitis.
abstract: Scattered evidence suggests that the human peritoneal cavity contains cells of the dendritic cell (DC) lineage but their characterization is missing. Here, we report that the peritoneal cavity of normal subjects and of stable patients on peritoneal dialysis (PD) contains a population of CD14(+) cells that can differentiate into DCs or macrophages. Within this pool, we characterized a CD14(+)CD4(+) cell subset (2.2% of the peritoneal cells) fulfilling the definition of myeloid DC precursors or pre-DC1 cells. These cells expressed high levels of HLA-DR, CD13, CD33, and CD86, and low levels of CD40, CD80, CD83, CD123, CD209, TLR-2 and TLR-4. These cells retained CD14 expression until late stages of differentiation, despite concomitant up-regulation of DC-SIGN (CD209), CD1a, CD80 and CD40. Peritoneal pre-DC1 cells had endocytic capacity that was down-regulated upon LPS/IFN-gamma stimulation, were more potent allo-stimulators than peritoneal CD14(+)CD4(-/lo) cells and monocyte-derived macrophages, and induced Th1 cytokine responses. More importantly, the number of peritoneal pre-DC1 cells increased during PD-associated peritonitis, with a different profile for Gram positive and Gram negative peritonitis, suggesting that these cells participate in the induction of peritoneal adaptive immune responses, and may be responsible for the bias towards Th1 responses during peritonitis.
authors.affiliation: The FOCIS Centre for Clinical Immunology and Immunotherapeutics, Robarts Research Institute, London, Ontario, Canada.
authors.forename: M L
authors.initials: ML
authors.lastname: McCully
authors.forename: T A
authors.initials: TA
authors.lastname: Chau
authors.forename: P
authors.initials: P
authors.lastname: Luke
authors.forename: P G
authors.initials: PG
authors.lastname: Blake
authors.forename: J
authors.initials: J
authors.lastname: Madrenas
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D016022:Case-Control Studies; D002454:Cell Differentiation; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D004705:Endocytosis; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D018950:Lipopolysaccharide Receptors / Q000276:immunology*; D018655:Lymphocyte Count; D008264:Macrophages / Q000276:immunology; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D010530:Peritoneal Dialysis / Q000009:adverse effects; D010537:Peritoneum / Q000276:immunology*; D010538:Peritonitis / Q000209:etiology / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology
chemical_list: D016207:Cytokines; D018950:Lipopolysaccharide Receptors
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