High efficiency opsonin-independent phagocytosis of Candida parapsilosis by human neutrophils

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 C. albicans. Immunofluorescence assays with β-glucan specific antibody detected more surface exposed β-glucan on C. parapsilosis than C. albicans. However, blockade of the β-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 difference 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 mechanism of toxicity. 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.

Candida parapsilosisand the neonate: epidemiology, virulence and host defense in a unique patient setting

“…Human neutrophils underwent phagocytosis and killing of C. parapsilosis much more efficiently than C. albicans yeast, suggesting that these interactions have properties that are unique among different Candida spp. [82]. Despite the increased susceptibility of preterm neonates to infection with C. parapsilosis , neutrophils from these patients responded to Candida in a similar fashion to adult cells [83].…”

“…Neutrophil phagocytosis of C. albicans is mediated in part via β-glucan recognition by dectin-1 and complement receptor 3 [84–87], although there is an ongoing controversy about the contribution of each receptor. Neutrophil phagocytosis of C. parapsilosis , however, does not appear to be mediated by dectin-1 or complement receptor 3, as neutrophil treatment with blocking antibodies against both receptors did not inhibit phagocytosis [82]. Current work from our group has demonstrated that the lectin galectin-3 plays an important role in the increased efficiency of neutrophil phagocytosis of C. parapsilosis versus C. albicans [Linden et al ., The role of galectin-3 in the human neutrophil response to candida and protection against disseminated candidiasis (2012), Submitted].…”

“…Considerably less attention has been focused on the specific developmental deficiencies in immune function that increase the risk for fungal disease. Because quantitative or qualitative defects in neutrophil function, for example, are known to contribute to invasive fungal infection, yet neonates who develop these infections are rarely neutropenic, our group tested specific adult and infant neutrophil functions when confronted with C. parapsilosis and C. albicans [82,83]. No significant differences among preterm infant, term infant or adult neutrophils were detected in these studies, but unexpected, dramatic differences in phagocytosis efficiency of these two species were observed.…”

Beyond Candida albicans: Mechanisms of immunity to non-albicans Candida species

“…We recently demonstrated that Dectin1 −/− mice were more susceptible to disseminated C. tropicalis infection than WT mice [22]. Little is known about whether dectin-1 participates in immunity to other NAC species, although phagocytosis of C. parapsilosis by neutrophils was not impaired following dectin-1 blockade in vitro [40]. Similarly, no difference in binding of C. glabrata was detected between WT and dectin-1 −/− bone marrow macrophages [41].…”

“…Several NAC species appear to be killed more efficiently than C. albicans [40, 85–87]. For example, killing of C. tropicalis , C. parapsilosis , C. krusei and C. glabrata by human neutrophils was higher than C. albicans killing [85, 86].…”