Original Paper

The Malassezia Sympodialis Allergen Mala s 11 Induces Human Dendritic Cell Maturation, in Contrast to Its Human Homologue Manganese Superoxide Dismutase
Monica Vilhelmsson^a, Catharina Johansson^a, Gunilla Jacobsson-Ekman^a, Reto Crameri^b, Arezou Zargari^a, Annika Scheynius<sup>a

a</sup>Karolinska Institutet, Department of Medicine, Clinical Allergy Research Unit, Stockholm, Sweden;
^bSwiss Institute of Allergy and Asthma Research (SIAF), Davos, Switzerland

Address of Corresponding Author

Int Arch Allergy Immunol 2007;143:155-162 (DOI: 10.1159/000099082)

  Key Words

• Allergen
• Dendritic cells
• Malassezia sympodialis
• Manganese superoxide dismutase

  Abstract

Background: Recently, we identified a major Malassezia sympodialis allergen, Mala s 11, which displays a high degree of DNA sequence homology to human manganese superoxide dismutase (hMnSOD). In atopic eczema patients sensitized to M. sympodialis, hMnSOD can elicit eczematous reactions and positive skin prick tests, suggesting cross- reactivity to Mala s 11 based on molecular mimicry. The objective of the current study was to compare the influence of Mala s 11 and hMnSOD on human dendritic antigen-presenting cells. Methods: Monocyte-derived dendritic cells (MDDCs) from healthy blood donors were co-cultured with recombinant Mala s 11 (rMala s 11), recombinant hMnSOD (rhMnSOD), lipopolysaccharide or cultured in medium alone. Phenotypic changes were analysed using flow cytometry and allogeneic lymphocyte proliferation assays. Cytokine release into culture supernatants was investigated using cytometric bead array. Results: Whereas rhMnSOD did not affect the MDDC phenotype, rMala s 11 up-regulated the maturation marker CD83, the co-stimulatory molecules CD40, CD80, CD86 and HLA-DR to a similar extent as lipopolysaccharide. Furthermore, rMala s 11, but not rhMnSOD, induced significantly higher levels of TNF-, IL-6, IL-8, IL-10 and IL-12p70 in the culture supernatants at 24 h in comparison with MDDCs cultured in medium alone. Finally, MDDCs pre-incubated with rMala s 11 induced a significantly higher proliferation of allogeneic CD14-depleted peripheral blood monocytes than MDDCs pre-incubated with rhMnSOD. Conclusion: Our results suggest that Mala s 11, but not hMnSOD, affects the immune response of healthy individuals through dendritic cell maturation and cytokine release. This indicates that dendritic cells possess the ability to distinguish between Mala s 11 and its human homologue MnSOD.

Copyright © 2007 S. Karger AG, Basel

  Author Contacts

Correspondence to: Dr. Monica Vilhelmsson
Department of Medicine, Clinical Allergy Research Unit
Karolinska University Hospital Solna, L2:04
SE-171 76 Stockholm (Sweden)
Tel. +46 8 517 766 96, Fax +46 8 33 57 24, E-Mail monica.vilhelmsson@ki.se

  Article Information

Received: July 11, 2006
Accepted after revision: November 20, 2006
Published online: January 26, 2007
Number of Print Pages : 8
Number of Figures : 2, Number of Tables : 1, Number of References : 28