Human dendritic cells are less potent at killing Candida albicans than both monocytes and macrophages.
ABSTRACT Dendritic cells (DC) function as professional phagocytes to kill Candida albicans and subsequently present it to the adaptive immune system. Monocytes, macrophages and DC were generated from five individual donors and their Candida-killing capacity and cytokine release were assessed. Compared to monocytes and macrophages, DC from healthy volunteers were significantly less effective in C. albicans--stimulated cytokine release, killing of C. albicans blastoconidia and damaging of C. albicans hyphae. In conclusion, while important as antigen-presenting cells and initiators of the adaptive immune system, DC are poor in both intracellular killing and damaging of C. albicans hyphae. Effective handling of large numbers of C. albicans is the prime task of the innate immune system consisting of large numbers of neutrophils and monocytes.
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ABSTRACT: Infections caused by Candida spp. continue to be a substantial cause of disease burden, especially in immunocompromised patients. New approaches are needed to improve the outcome of patients suffering from Candida infections, because it seems unlikely that the established standard treatment will drastically lower the morbidity of mucocutaneous Candida infections and the high mortality associated with invasive candidiasis. New insights into the mechanisms of the anti-Candida host response have contributed to the design of novel immunotherapeutic approaches that have been proposed as adjuvant therapy in Candida infections. This review presents an overview of novel strategies in the prevention and treatment of Candida infections, with a special focus on adjuvant immunotherapy.FEMS microbiology reviews 11/2010; 34(6):1063-75. DOI:10.1111/j.1574-6976.2010.00232.x · 13.81 Impact Factor
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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.FEMS Immunology & Medical Microbiology 10/2007; 51(1):70-83. DOI:10.1111/j.1574-695X.2007.00278.x · 2.55 Impact Factor
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ABSTRACT: Membrane traffic in activated macrophages is required for two critical events in innate immunity: proinflammatory cytokine secretion and phagocytosis of pathogens. We found a joint trafficking pathway linking both actions, which may economize membrane transport and augment the immune response. Tumor necrosis factor alpha (TNFalpha) is trafficked from the Golgi to the recycling endosome (RE), where vesicle-associated membrane protein 3 mediates its delivery to the cell surface at the site of phagocytic cup formation. Fusion of the RE at the cup simultaneously allows rapid release of TNFalpha and expands the membrane for phagocytosis.Science 01/2006; 310(5753):1492-5. DOI:10.1126/science.1120225 · 31.48 Impact Factor