The study of macrophage heterogeneity in the peritoneal cavity
Mononuclear phagocytes play a key role in tissue homeostasis and in host defense\ud against pathogen invasion. However, the phenotypic identities and functional\ud properties of this heterogeneous population within the peritoneal cavity remains\ud poorly elucidated. In the context of peritoneal dialysis, it is hypothesized that the\ud modification of macrophage/dendritic cell biology by the dialysis process would alter\ud tissue homeostasis, host susceptibility to infection and local immunity, compromising\ud long-term outcomes of the patients. The research work carried out in this thesis has\ud tested this hypothesis by examination of the immunobiology (mainly phenotype and\ud function) of human and murine peritoneal macrophage and dendritic cell subsets.\ud Moreover, the potential link between the altered immunobiology of peritoneal\ud mononuclear phagocytes and clinical outcomes of the dialysis patients has been\ud investigated. Several key findings were generated during these studies: 1) multiple\ud discrete peritoneal macrophage and dendritic cell subsets have been phenotypically\ud identified in humans (from different clinical settings of peritoneal dialysis) and in\ud mice (from naïve and inflamed conditions); 2) in humans, the phenotypes and the\ud activation/maturation status of peritoneal macrophages and dendritic cells are\ud modified throughout the dialysis course and also during acute peritonitis; some\ud characteristic alterations are associated with adverse patient outcomes; 3) in mice, the\ud distinctive kinetics of the respective peritoneal macrophage and dendritic cell subsets\ud in clinically relevant acute peritonitis models have been characterized; 4) individual\ud peritoneal macrophage and dendritic cell subsets (human and mice) display\ud differences in their phagocytic capacity and the ability to process and present antigen.
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