Uptake of the yeast Malassezia furfur and its allergenic components by human immature CD1a+ dendritic cells

Background Atopic dermatitis (AD) is a chronic inflammatory skin disease with increasing prevalence, though still little is known of the pathomechanisms and the causes of the disease. Patients with AD often have specific IgE reactivity to the yeast Malassezia furfur (M. furfur), present in the normal microflora on human skin. Objective To investigate the possible interaction of immature and mature antigen-presenting dendritic cells with the yeast M. furfur and its allergenic components. Methods Monocyte-derived dendritic cells (MDDCs) generated from human peripheral blood were allowed to interact with FITC-labelled whole M. furfur yeast cells, M. furfur extract, a recombinant allergen from M. furfur designated rMal f 5 and M. furfur mannan, in the absence of IgE antibodies. Interaction and uptake were detected using flow cytometry and confocal laser scanning microscopy. Results Internalization of M. furfur yeast cells and yeast components by immature MDDCs was found using confocal laser scanning microscopy. Results from flow cytometric studies showed that a median of 94% (range, 65-98%) of the immature CD1a(+) MDDCs were M. furfur extract positive, 81% (75-97%) rMal f 5 positive and 93% (62-98%) mannan positive. Mature CD1a(+) MDDCs were significantly less efficient in this respect, with the corresponding figures only 26% (6-37%, P < 0.01), 6% (2-15%, P < 0.05) and 32% (9-50%, P < 0.01), respectively. Uptake of the non-glycosylated rMal f 5 by immature CD1a(+) MDDCs was decreased to 27% (15-38%) by inhibition of pinocytosis. The binding of M. furfur extract and mannan was inhibited in a dose-dependent manner by methyl-<alpha>-D-mannopyranoside, suggesting uptake via the mannose receptor. Conclusion Human immature CD1a(+) MDDCs can efficiently take up M. furfur and allergenic components from the yeast in the absence of IgE antibodies, implying that sensitization of AD patients to M. furfur can be mediated by immature dendritic cells in the skin.