The Malassezia sympodialis Allergen Mala s 11 with Sequence Similarity to Manganese Superoxide Dismutase Induces Maturation and Production of Inflammatory Cytokines in Human Dendritic Cells

The chronic inflammatory skin disease atopic eczema (AE) affects almost 15% of the population in many countries today. The pathogenesis of AE is not fully understood. A combination of genetic predisposition and environmental factors like microorganisms seems to contribute to the symptoms. The yeast Malassezia sympodialis is part of our normal skin micro flora but can act as an allergen and elicit specific IgE and T-cell reactivity in patients with AE. Recently, we identified a novel major M. sympodialis allergen, designated Mala s 11 (22.4 kDa), with sequence similarity to the mitochondrial enzyme manganese superoxide dismutase (MnSOD). Interestingly, Mala s 11 has a high degree of homology to human MnSOD. The aim of this study was to examine the effects of recombinant Mala s 11 on antigen-presenting dendritic cells. Monocyte-derived dendritic cells (MDDCs) from healthy blood donors were cultured with or without Mala s 11 for different time periods. It was found that the maturation marker CD83 and the costimulatory molecules CD80 and CD86 were upregulated on the MDDCs exposed to Mala s 11 for 24 h, as demonstrated by flow cytometry. Furthermore, coculture of MDDCs with Mala s 11 for 9 h induced an increased production of the inflammatory cytokines IL-6 (200-fold), TNF-α (100-fold) and IL-8 (sixfold), as detected by the cytometric bead array (CBA) analysis. Our results suggest that Mala s 11 affects the immune response through DC maturation and production of inflammatory cytokines. The potential cross-reactivity with human MnSOD needs to be explored and the exact role of Mala s 11 in the pathogenesis of AE assessed in clinical studies involving skin prick and atopy patch tests.