Human dendritic cells are less potent at killing Candida albicans than both monocytes and macrophages

Department of Medicine, University Medical Center St. Radboud, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands.
Microbes and Infection (Impact Factor: 2.86). 10/2004; 6(11):985-9. DOI: 10.1016/j.micinf.2004.05.013
Source: PubMed


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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    • "Although human DCs can phagocytose and eliminate C. albicans cells [15], there is little information regarding the outcome of the interactions between DCs and C. parapsilosis cells. Therefore, we examined the ability of human monocyte-derived DCs to phagocytose C. parapsilosis. "
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    ABSTRACT: Candida parapsilosis typically is a commensal of human skin. However, when host immune defense is compromised or the normal microflora balance is disrupted, C. parapsilosis transforms itself into an opportunistic pathogen. Candida-derived lipase has been identified as potential virulence factor. Even though cellular components of the innate immune response, such as dendritic cells, represent the first line of defense against invading pathogens, little is known about the interaction of these cells with invading C. parapsilosis. Thus, the aim of our study was to assess the function of dendritic cells in fighting C. parapsilosis and to determine the role that C. parapsilosis-derived lipase plays in the interaction with dendritic cells. Monocyte-derived immature and mature dendritic cells (iDCs and mDCs, respectively) co-cultured with live wild type or lipase deficient C. parapsilosis strains were studied to determine the phagocytic capacity and killing efficiency of host cells. We determined that both iDCs and mDCs efficiently phagocytosed and killed C. parapsilosis, furthermore our results show that the phagocytic and fungicidal activities of both iDCs and mDCs are more potent for lipase deficient compared to wild type yeast cells. In addition, the lipase deficient C. parapsilosis cells induce higher gene expression and protein secretion of proinflammatory cytokines and chemokines in both DC types relative to the effect of co-culture with wild type yeast cells. Our results show that DCs are activated by exposure to C. parapsilosis, as shown by increased phagocytosis, killing and proinflammatory protein secretion. Moreover, these data strongly suggest that C. parapsilosis derived lipase has a protective role during yeast:DC interactions, since lipase production in wt yeast cells decreased the phagocytic capacity and killing efficiency of host cells and downregulated the expression of host effector molecules.
    BMC Microbiology 05/2011; 11(1):122. DOI:10.1186/1471-2180-11-122 · 2.73 Impact Factor
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    • "Proinflammatory cytokines such as tumor necrosis factor a (TNFa) and interleukin (IL)-1b are crucial for the proper activation of PMNs. TNFa is essential for anti-Candida host defense through the recruitment of neutrophils and phagocytosis , and deficiency results in higher mortality during experimental disseminated candidiasis (Netea et al., 2004). "
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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 · 13.24 Impact Factor
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    • "In addition to their ability to ingest and kill pathogens, mononuclear phagocytes are responsible for stimulating additional innate and adaptive immune responses through cytokine secretion (Underhill & Ozinsky, 2002). Monocytes encounter the organism early in infection, and were found to be more effective at killing C. albicans than dendritic cells or macrophages (Netea et al., 2004a). Monocytes exposed to C. albicans produce tumor necrosis factor-a (TNF-a) which is required for surviving systemic candidiasis (Netea et al., 1999). "
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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 · 3.08 Impact Factor
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