The allergenic yeast Malassezia furfur induces maturation of human dendritic cells

Background The yeast Malassezia furfur (M. furfur), present in the normal m icroflora of human skin, can act as an allergen that incites specific IgE r eactivity and T cell proliferation in atopic dermatitis (AD) patients. The role of antigen presenting dendritic cells (DCs) in the onset and maintenan ce of AD is not well established. Objective The objective of the present study was to assess whether the inte raction of M. furfur with human DCs will result in DC maturation, cytokine production and lymphocyte proliferation. Methods Monocyte-derived dendritic cells (MDDCs) were generated from human peripheral blood. Immature MDDCs were cultured with or without M. furfur or plastic beads, and with or without CD40L stimulation. Interaction of yeast cells by MDDCs was studied by time-lapse photography and cytokines were de tected in culture supernatants with ELISA. The ability of MDDCs pre-incubat ed with M. furfur to induce proliferation in autologous lymphocytes was mea sured by [H-3]-thymidine incorporation. Results Time-lapse photography showed that the majority of immature MDDCs i nternalized whole M. furfur yeast cells within 1 h. The presence of M. furf ur induced maturation (CD83 expression) of MDDCs, and up-regulation of the costimulatory molecules CD80 and CD86. Production of TNF-alpha, IL-1 beta a nd IL-18 by MDDCs increased significantly (P < 0.05 for TNF-<alpha> and IL- 1 beta, and P < 0.01 for IL-18) after the addition of M. furfur, while IL-1 0 and IL-12p70 levels remained unaltered. The CD40L-stimulated IL12p70 prod uction by MDDCs was decreased in the presence of M. furfur (P < 0.05). Fina lly, immature MDDCs pre-incubated with M. furfur induced a proliferative re sponse in autologous CD14-depleted peripheral blood mononuclear cells, in a dose-dependent manner. Conclusion The data indicate that immature MDDCs can internalize the opport unistic yeast M. furfur. This process was associated with MDDC maturation, production of proinflammatory and immunoregulatory cytokines, which might f avour induction of a Th2-type immune response, and a capacity to stimulate lymphocyte proliferation. This chain of events most likely contributes to t he inflammatory reaction in AD.