The phagocytic capacity of macrophages and dendritic cells is an important feature during microbial infection, because the outcome of the interaction of phagocytic cells with fungal pathogens influences the susceptibility of the host to the infection [16, 17]. In this work we demonstrate that the emerging fungal pathogen C. parapsilosis can be efficiently phagocytosed and killed by human monocyte derived dendritic cells. Our results showed that after 1 h co-incubation 29.4% of iDC and 24.8% of mDC had ingested C. parapsilosis wild type cells. Interestingly, in a comparable study, approximately 60% of a given iDC population phagocytose C. albicans  thus, C. parapsilosis cells induce less phagocytosis in comparison to C. albicans. In addition, we also observed that lipase deficient C. parapsilosis cells were more efficiently ingested by iDCs and mDCs relative to wild type yeast. The microscopy and FACS results demonstrating avid DC phagocytosis of both wild type and lipase deficient yeast is consistent with an activated phenotype of these host effector cells. Moreover, the enhanced phagocytosis of lipase deficient C. parapsilosis by DCs relative to wild type yeast cells suggests that lipase interferes with efficient DC activation.
Dendritic cells are able to kill internalized fungal cells. The in vitro infections of DCs resulted in a 12% killing of C. parapsilosis wild type cells. This result is comparable with that of C. albicans (13.6 ± SD 5.4%) . Moreover, DCs did not kill C. albicans cells as efficiently as monocytes or macrophages , and the C. albicans findings and our results are consistent with the concept that the function of DC is to present candidal antigens to T-cells  rather than to eliminate the microorganism. Notably, our data showed a significantly elevated killing capacity of human dendritic cells against lipase deficient C. parapsilosis strain. In summary, DCs can effectively phagocytose C. parapsilosis, but the capacity to kill the yeast cells is less than that of macrophages  and according to our recent results, fungal lipase suppresses the fungicidal activity of DCs.
The mechanisms involved in intracellular pathogenesis are diverse. Among fungi, the most studied intracellular pathogen is Histoplasma capsulatum, which is able to impair phagosome-lysosome fusion [20, 21]. In the case of C. parapsilosis wild type strain, we observed that there is a defect in the maturation of the DC phago-lysosome using lysosomal markers of this process. This finding is in agreement with the related species C. albicans, where alterations of phagosome maturation and acidification defects have been described [22, 23]. The lipase deficient mutants showed higher co-localization with lysotracker stain, suggesting more frequent phago-lysosome fusion and compartment acidification. In addition, our findings highlight that secreted fungal lipases appear to have a role in the protective mechanisms against the host intracellular killing processes.
The immune system may be activated by the recognition of nonself molecules of infectious agents or by recognition of danger signals that include host molecules released by damaged host cells . It is proposed that the two models are compatible, which may also be the case in our model: both C. parapsilosis strains induced the expression of chemotactic molecules, in addition, DCs infected with lipase deficient yeast showed increased cell death which is known to be accompanied by the release of danger signals . Consequently, we propose that DCs infected with lipase deficient yeast cells activate more robust immune response.
Although both wild type and lipase deficient C. parapsilosis induced strong, time-dependent activation of pro-inflammatory genes such as IL-1α, IL-6, TNF-α, and CXCL-8 in both DC types, lipase deficient yeast induced significantly higher gene expression of effector molecules. Since locally produced chemotactic factors are presumed to mediate the sequence of events leading to the infiltration of immune cells at inflammatory sites, local expression of pro-inflammatory mediators after contact with C. parapsilosis could have an initiator role in the attraction of additional immune cells to the sites of infection. This is supported by the fact that CXCL8 is one of the most potent neutrophil chemoattractants  that affects not only the recruitment of neutrophils into the tissues but also modulates the ability of these neutrophils to cross epithelial barriers and to kill pathogens. In addition, TNF-α enhances the fungicidal properties of neutrophils, promotes the adhesion of immune to endothelial cells and acts as a danger signal. Corresponding to this finding, we found that DCs infected with lipase deficient yeast cells displayed increased protease activity, which accompanies cell death and the release of danger signals. Finally, TNF-α, IL-1α and IL-6 are also implicated in the induction of antimicrobial peptide expression in epithelial cells . Taken together, the secretion of pro-inflammatory mediators and the release of danger signals by DCs as a response to C. parapsilosis may play a crucial role in the recruitment of immune cells into the sites of infection.