Science and Clinical Practice
E-Book, Englisch, 319 Seiten, eBook
ISBN: 978-3-642-03616-3
Verlag: Springer
Format: PDF
Kopierschutz: Wasserzeichen (»Systemvoraussetzungen)
Zielgruppe
Professional/practitioner
Autoren/Hrsg.
Weitere Infos & Material
Introduction: Malassezia Yeasts from a Historical Perspective.- Biodiversity, Phylogeny and Ultrastructure.- Epidemiology of Malassezia-Related Skin Diseases.- Physiology and Biochemistry.- Malassezia Species and Immunity: Host–Pathogen Interactions.- Pityriasis Versicolor and Other Malassezia Skin Diseases.- Malassezia Yeasts in Seborrheic and Atopic Eczemas.- Malassezia Fungemia, Antifungal Susceptibility Testing and Epidemiology of Nosocomial Infections.- Genomics and Pathophysiology: Dandruff as a Paradigm.- Malassezia Yeasts in Animal Disease.- Malassezia Database.
"5.3.4 Cellular Responses and Cytokine Production (p.144-145)
Phagocytes form an important part of the innate immune defence against fungi and the interaction of neutrophils and Malassezia has been examined in several studies. The uptake and killing of Malassezia by neutrophils in vitro is a complement-dependent process [67]. Uptake is maximal at 40 min, after which it plateaus, but killing of the ingested yeast is very inefficient, with only 5% of the cells killed after 2 h. This lack of killing is in contrast to other yeast and fungal genera, where killing of up to 80% of cells occurs [68, 69]. In this study, if Malassezia cells were pre-treated with ketoconazole, killing increased to 23%, with the amount of killing proportional to increasing drug concentrations. Several possible explanations have been proposed for this inability of neutrophils to kill Malassezia.
When grown in the presence of oleic acid, Malassezia produces azelaic acid, a C9 dicarboxylic acid [70]. Azelaic acid decreases production of O2 - and OH. by neutrophils in a dosedependent manner and also reduces H2O2 production, due to inhibition of cellular metabolism [71]. It is also an oxygen radical scavenger [72], and if azelaic acid is produced by Malassezia in vivo, this may help to protect it from the oxygen-dependent killing mechanisms used by neutrophils. Another factor that has been suggested to help protect Malassezia from phagocytic killing is the presence of a lipid-rich capsular-like layer around the yeast cells [73].
Preliminary data suggest that the capsular-like layer reduced Malassezia uptake and activation of neutrophils and that this may contribute to their protection during phagocytosis [74]. More recently, the role of some of the tryptophan metabolites of Malassezia yeasts in this lack of neutrophil activity against Malassezia have been demonstrated [75]. M. furfur can convert tryptophan into a range of indole alkaloids, including the pityriarubins (A, B and C).
Neutrophils were obtained from healthy donors and stimulated with a calcium ionophore to stimulate superoxide release. When the pityriarubins were added, they caused a decrease in the production of reactive oxygen species (ROS) in a concentration dependent manner, with pityriarubin C being most active in the assay. The authors concluded that this ability to produce such compounds would enable Malassezia to downregulate the immune response directed against it and contribute to the lack of inflammation seen in PV.
Binding between Malassezia and phagocytic cells has been studied in the human monocytic cell line THP-1, and is mediated by the mannose receptor, b-glucan receptor and complement receptor 3 [76]. When the THP1 cells were stimulated with live or heat-killed Malassezia cells, the production of IL8 increased in a time and concentration-dependent pattern [77]. Stimulation of the granulocyte cell line, HL60, by Malassezia increased the levels of both IL8 and IL1a, again in a time and concentration dependent pattern.
This stimulation of monocytic cells by Malassezia and the resultant production of IL8 and IL1a will lead to the chemotaxis of neutrophils and T-cells and hence augment the inflammatory response. Chemoattraction of neutrophils from psoriatic, atopic and healthy controls in response to Malassezia was studied by Bunse et al. [78]. Using a Boyden chamber, cells of M. furfur were incubated in the lower part of the chamber, with the test neutrophils in the upper part and after three hours, the neutrophils that had crossed the membrane separating the two parts of the chamber were counted."
