Abstract
Candida species are associated with invasive fungal infections, and C. parapsilosis has become increasingly prevalent. As key antifungal effector cells, the function of human neutrophils confronting C. parapsilosis was investigated. We hypothesized that interaction between neutrophils and Candida species may not be uniform. Opsonins were omitted from these studies to understand the antifungal mechanisms at their most basic level. Human neutrophils underwent phagocytosis of C. parapsilosis with much higher efficiency than with C. albicans. Immunofluorescence assays with ß-glucan specific antibody detected more surface exposed ß-glucan on C. parapsilosis than C. albicans. However, blockade of the ß-glucan receptor Dectin-1, reduced phagocytosis of C. albicans but not C. parapsilosis. Inclusion of excess β-glucan, mannan, or chitin also had no effect on phagocytosis of C. parapsilosis. Consistent with the differences noted in phagocytosis, neutrophils mediated damage to C. parapsilosis but not C. albicans in assays of residual metabolic activity. C. parapsilosis was more sensitive to oxidative stress, and inclusion of antioxidant in toxicity assays decreased neutrophil mediated damage, suggesting that generation of reactive oxygen species contributes to the toxicity mechanism. These data suggest that the interaction between neutrophils and Candida species is not uniform and may partially account for differences observed in the epidemiology and natural history of infections caused by these species.
Acknowledgements
We thank Jonathan Reichner and Liz Lavigne for providing mAb BF-Div and for helpful discussions. We thank Gordon Brown for providing mAb GE2, and Sunil Shaw for assistance with FACS analysis. This work was supported in part by Basil O’Connor Starter Scholar Research Award Grant No. 5-FY05-1211 from the March of Dimes Foundation, a National Institute of Health grant (K08 AI064919), and a NIH COBRE grant (P20 RR018728).
Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
This paper was first published online on Early Online on 01 February 2010.