title: Immunomodulatory properties of antifungal agents on phagocytic cells.
abstract: Phagocytic cells, particularly neutrophils and monocytes/macrophages, are the first line and the most effective form of innate host defence against pathogenic fungi. During antifungal therapy these phagocytic cells are also exposed to antifungal agents. In the phagocyte-fungus-antifungal agent interplay, drugs may directly interact with phagocytes through specific pattern recognition receptors, leading to altered antifungal activities. Antifungal agents, through modulation of fungal virulence, may initiate different immune response programs in the phagocytes, leading to antifungal synergism/antagonism or up-regulation of gene expression for a pro-inflammatory response. Additionally, indirect modulation of phagocyte behavior by pretreatment of neutrophils, monocytes, and macrophages with cytokines and exposure to antifungal agents have shown promising findings for combined drug-cytokine therapy that may improve treatment of life-threatening fungal diseases. In this review, we discuss the main in vitro and in vivo immunomodulatory effects of antifungal agents on phagocytes in response to pathogenic fungi, as well as we address underlying immunopharmacologic mechanisms and their potential impact on clinical outcome.
authors: Laboratory of Infectious Diseases, 3rd Department of Paediatrics, School of Medicine, Aristotle University, Hippokration Hospital, Thessaloniki, Greece.
authors: Maria
authors: M
authors: Simitsopoulou
authors: Emmanuel
authors: E
authors: Roilides
authors: Thomas J
authors: TJ
authors: Walsh
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000276:immunology / Q000494:pharmacology*; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D005658:Fungi / Q000187:drug effects* / Q000472:pathogenicity; D006801:Humans; D007155:Immunologic Factors / Q000276:immunology / Q000494:pharmacology*; D051379:Mice; D009181:Mycoses / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology; D010586:Phagocytes / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D051192:Receptors, Pattern Recognition / Q000187:drug effects / Q000378:metabolism
chemical_list: D000935:Antifungal Agents; D016207:Cytokines; D007155:Immunologic Factors; D051192:Receptors, Pattern Recognition