title: Differential interaction of the two related fungal species Candida albicans and Candida dubliniensis with human neutrophils.
abstract: Candida albicans, the most common facultative human pathogenic fungus is of major medical importance, whereas the closely related species Candida dubliniensis is less virulent and rarely causes life-threatening, systemic infections. Little is known, however, about the reasons for this difference in pathogenicity, and especially on the interactions of C. dubliniensis with the human immune system. Because innate immunity and, in particular, neutrophil granulocytes play a major role in host antifungal defense, we studied the responses of human neutrophils to clinical isolates of both C. albicans and C. dubliniensis. C. dubliniensis was found to support neutrophil migration and fungal cell uptake to a greater extent in comparison with C. albicans, whereas inducing less neutrophil damage and extracellular trap formation. The production of antimicrobial reactive oxygen species, myeloperoxidase, and lactoferrin, as well as the inflammatory chemokine IL-8 by neutrophils was increased when stimulated with C. dubliniensis as compared with C. albicans. However, most of the analyzed macrophage-derived inflammatory and regulatory cytokines and chemokines, such as IL-1α, IL-1β, IL-1ra, TNF-α, IL-10, G-CSF, and GM-CSF, were less induced by C. dubliniensis. Similarly, the amounts of the antifungal immunity-related IL-17A produced by PBMCs was significantly lower when challenged with C. dubliniensis than with C. albicans. These data indicate that C. dubliniensis triggers stronger early neutrophil responses than C. albicans, thus providing insight into the differential virulence of these two closely related fungal species, and suggest that this is, in part, due to their differential capacity to form hyphae.
authors.affiliation: Junior Research Group Cellular Immunobiology, Leibniz Institute for Natural Product Research and Infection Biology-Hans Knöll Institute, D-07745 Jena, Germany.
authors.forename: Eliska
authors.initials: E
authors.lastname: Svobodová
authors.forename: Peter
authors.initials: P
authors.lastname: Staib
authors.forename: Josephine
authors.initials: J
authors.lastname: Losse
authors.forename: Florian
authors.initials: F
authors.lastname: Hennicke
authors.forename: Dagmar
authors.initials: D
authors.lastname: Barz
authors.forename: Mihály
authors.initials: M
authors.lastname: Józsi
mesh_terms: D002176:Candida albicans / Q000276:immunology* / Q000378:metabolism / Q000472:pathogenicity; D002177:Candidiasis / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002450:Cell Communication / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D006801:Humans; D009504:Neutrophils / Q000276:immunology* / Q000382:microbiology* / Q000469:parasitology; D010587:Phagocytosis / Q000276:immunology; D013045:Species Specificity; D014774:Virulence / Q000276:immunology