In vitro interactions of Candida parapsilosis wild type and lipase deficient mutants with human monocyte derived dendritic cells

Abstract

BackgroundCandida 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.ResultsMonocyte-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.ConclusionsOur 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.

Candida parapsilosis Secreted Lipase as an Important Virulence Factor

“…Intracellular survival of C. parapsilosis cells following phagocytosis has been recently reported [35]. In contrast with DCs, no difference was detected in the phagocytic efficiency of fungal cells by PBMC-DMs, although early phago-lysosome fusion was detected in both cases [33,55]. These results led to the conclusion that fungal lipase secretion delays phagosome maturation, thus is considered to be one of the factors that contribute to fungal survival inside host cells.…”

“…2) [34]. Subsequent studies with human peripheral blood mononuclear cell -derived macrophages (PBMC-DMs) [33] and dendritic cells (DCs) [55] reported similar outcomes. Overall, the Cp ΔΔlip1-ΔΔlip2 strain appeared to be less virulent, as both types of human primary cells were able to kill mutant cells in a higher ratio compared to wild type cells.…”

“…Similarly, higher levels of IL-8 and COX-2 expression were observed when PBMC-DMs were treated with the lipase deficient mutant in comparison with wild type strain. Interestingly, the anti-inflammatory response of PBMC-DM was also modulated, as an elevated IL-10 level was found after exposure to Cp ΔΔlip1-ΔΔlip2 compared to that occurring after challenge with wild type yeast [33,55].…”

“…Cyclooxygenase 2 (COX-2) is essential for the synthesis of the biologically active inflammation inducer prostaglandin E2 [48]. Toth A. et al and Nagy and Filkor et al reported that both DCs and PBMC-DMs released IL-1, IL-6 and TNFα pro-inflammatory cytokines at a markedly increased level in the presence Cp ΔΔlip1-ΔΔlip2 cells compared to that occurring in the presence of wild type yeast cells and an elevated level of IL-8 was detected after DCs were challenged with Cp ΔΔlip1-ΔΔlip2 compared to wild type cells [55]. Similarly, higher levels of IL-8 and COX-2 expression were observed when PBMC-DMs were treated with the lipase deficient mutant in comparison with wild type strain.…”

“…1) [33,34,55,56]. Initial studies focused on the interactions of C. parapsilosis with murine macrophages.…”