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
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.
Available from: Narciso Almeida Vieira
- "While neutrophils are crucial to eliminate the fungi via phagocytosis, macrophages/monocytes are key cells in the development of adaptive cellular response, mainly via cytokine production3233343536373839. Although neutrophils are key players in the phagocytosis of Candida spp.,Netea et al.showed that macrophages/monocytes are also able to kill yeasts and damage C. albicans hyphae in a similar manner among them, and more efficiently than dendritic cells. Another study reported the ability of monocytes to kill hyphae, but less efficiently than phagocytized yeasts. However, the candidacidal function of monocytes can be modulated by some cytokines[42,43]. "
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ABSTRACT: Candida-associated denture stomatitis (DS) is the most frequent lesion among denture wearers, especially the elderly. DS is strongly associated with Candida albicans, as well as local and systemic factors, such as impaired immune response. Monocytes are important in the protective immune response against the fungus by the production of cytokines that recruit and activate leukocytes. There are functional changes in these cells with age, and individual alterations involving monocyte response may predispose the host to developing infections by Candida spp. In this study, our aim was to evaluate the production of TNF-α, IL-6, CXCL8, IL-1β, MCP-1 and IL-10 by monocytes from elderly denture wearers with/without DS and elderly or young non-denture wearers. We detected that monocytes from elderly denture wearers with Candida-related denture stomatitis produced lower levels of CXCL-8, IL-6 and MCP-1. This imbalance in cytokine levels was observed in spontaneous or LPS-stimulated production. Therefore, our data suggested that inherent aspects of the host, such as changes in cytokine production by monocytes, might be associated with the development and the persistence of DS irrespective of aging.
Available from: Prashini Moodley
- "Whilst the production of pro-inflammatory cytokines can be normal, levels of anti-inflammatory cytokines are severely impaired in the TLR2 -/-mice. The authors found that this was accompanied by a substantial decrease in the CD4+CD25+ regulatory T (Treg) cell population in TLR2 -/mice (Netea et al., 2004). Furthermore, in vitro studies confirmed that enhanced survival of Treg cells was induced by TLR2 agonists; C. albicans induces immunosuppression through TLR2-derived signals that mediate increased anti-inflammatory cytokine (that is, IL- 10) production and survival of Treg cells, playing a critical role in the pathogenesis of symptomatic VVC. "
Available from: Csaba Vágvölgyi
- "Although human DCs can phagocytose and eliminate C. albicans cells , 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.
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