The Malassezia sympodialis allergen Mala s 11 induces human dendritic cell maturation, in contrast to its human homologue manganese superoxide dismutase.
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-alpha, 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.


CONCLUSIONS
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.
Vilhelmsson
Monica
M
Karolinska Institutet, Department of Medicine, Clinical Allergy Research Unit, Stockholm, Sweden. monica.vilhelmsson@ki.se
Johansson
Catharina
C
Jacobsson-Ekman
Gunilla
G
Crameri
Reto
R
Zargari
Arezou
A
Scheynius
Annika
A
D000485:Allergens / Q000276:immunology*; D015703:Antigens, CD / Q000378:metabolism; D000946:Antigens, Fungal / Q000276:immunology*; D018122:B7-1 Antigen / Q000378:metabolism; D051940:B7-2 Antigen / Q000378:metabolism; D019013:CD40 Antigens / Q000378:metabolism; D002478:Cells, Cultured; D003429:Cross Reactions; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology*; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism; D008290:Malassezia / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000378:metabolism; D010641:Phenotype; D011994:Recombinant Proteins / Q000276:immunology; D013482:Superoxide Dismutase / Q000276:immunology*; D000097802:CD83 Antigen
D000485:Allergens; D015703:Antigens, CD; D000946:Antigens, Fungal; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D019013:CD40 Antigens; D016207:Cytokines; D006684:HLA-DR Antigens; D007136:Immunoglobulins; D008562:Membrane Glycoproteins; D011994:Recombinant Proteins; D013482:Superoxide Dismutase; D000097802:CD83 Antigen