title: Monocyte responses to Candida albicans are enhanced by antibody in cooperation with antibody-independent pathogen recognition.
abstract: Although most individuals are colonized with Candida albicans, only patients with insufficient or nonfunctional phagocytes develop life-threatening C. albicans disease. Because recognition of bacterial pathogens through phagocyte receptors for IgG (FcgammaR) is known to augment phagocyte responses, we postulated that antibody opsonization would enhance monocyte damage to C. albicans and subsequent tumor necrosis factor-alpha (TNF-alpha) production. After exposure to the human monocytic cell line THP-1, opsonized yeast showed an 89% decrease in metabolic activity, compared with 40% for unopsonized yeast (P<0.05). Culture supernatants contained 1316 pg mL(-1) of TNF-alpha after monocytes were exposed to opsonized yeast vs. 341 pg mL(-1) for unopsonized yeast (P=0.003). Similar results were obtained using peripheral blood mononuclear cells. Antibody opsonization of C. albicans germ tubes enhanced TNF-alpha production but did not affect organism damage. Antibody-dependent and antibody-independent factors were found to act synergistically to increase TNF-alpha production. ERK activation was important for both antibody-dependent and antibody-independent stimulation of TNF-alpha production, but not for monocyte-mediated organism damage. These data suggest that FcgammaR cooperates positively with antibody-independent recognition mechanisms in what may be a novel link between innate and adaptive immunity to C. albicans.
authors.affiliation: Department of Pediatrics, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA. melanie_wellington@urmc.rochester.edu
authors.forename: Melanie
authors.initials: M
authors.lastname: Wellington
authors.forename: Kristy
authors.initials: K
authors.lastname: Dolan
authors.forename: Constantine G
authors.initials: CG
authors.lastname: Haidaris
mesh_terms: D000908:Antibodies, Fungal / Q000276:immunology*; D002176:Candida albicans / Q000276:immunology*; D002460:Cell Line; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology; D006801:Humans; D020935:MAP Kinase Signaling System; D009000:Monocytes / Q000276:immunology*; D010587:Phagocytosis; D010766:Phosphorylation; D051193:Toll-Like Receptors / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D000908:Antibodies, Fungal; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D048049:Extracellular Signal-Regulated MAP Kinases