title: The allergenic yeast Malassezia furfur induces maturation of human dendritic cells.
abstract: BACKGROUND
  The yeast Malassezia furfur (M. furfur), present in the normal microflora of human skin, can act as an allergen that incites specific IgE reactivity and T cell proliferation in atopic dermatitis (AD) patients. The role of antigen presenting dendritic cells (DCs) in the onset and maintenance of AD is not well established.
  
  
  OBJECTIVE
  The objective of the present study was to assess whether the interaction 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 detected in culture supernatants with ELISA. The ability of MDDCs pre-incubated with M. furfur to induce proliferation in autologous lymphocytes was measured by [(3)H]-thymidine incorporation.
  
  
  RESULTS
  Time-lapse photography showed that the majority of immature MDDCs internalized whole M. furfur yeast cells within 1 h. The presence of M. furfur induced maturation (CD83 expression) of MDDCs, and up-regulation of the costimulatory molecules CD80 and CD86. Production of TNF-alpha, IL-1 beta and 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-10 and IL-12p70 levels remained unaltered. The CD40L-stimulated IL12p70 production by MDDCs was decreased in the presence of M. furfur (P < 0.05). Finally, immature MDDCs pre-incubated with M. furfur induced a proliferative response in autologous CD14-depleted peripheral blood mononuclear cells, in a dose-dependent manner.
  
  
  CONCLUSIONS
  The data indicate that immature MDDCs can internalize the opportunistic yeast M. furfur. This process was associated with MDDC maturation, production of pro-inflammatory and immunoregulatory cytokines, which might favour induction of a Th2-type immune response, and a capacity to stimulate lymphocyte proliferation. This chain of events most likely contributes to the inflammatory reaction in AD.
authors.affiliation: Department of Medicine, Unit of Clinical Allergy Research, Karolinska Institutet and Hospital, Stockholm, Sweden. eva.buentke@ks.se
authors.forename: E
authors.initials: E
authors.lastname: Buentke
authors.forename: L C
authors.initials: LC
authors.lastname: Heffler
authors.forename: R P
authors.initials: RP
authors.lastname: Wallin
authors.forename: C
authors.initials: C
authors.lastname: Löfman
authors.forename: H G
authors.initials: HG
authors.lastname: Ljunggren
authors.forename: A
authors.initials: A
authors.lastname: Scheynius
mesh_terms: D000485:Allergens / Q000009:adverse effects*; D015703:Antigens, CD / Q000502:physiology; D023201:CD40 Ligand / Q000096:biosynthesis; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000166:cytology*; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology; D008290:Malassezia; D010865:Pilot Projects; D012016:Reference Values; D013997:Time Factors; D015003:Yeasts
chemical_list: D000485:Allergens; D015703:Antigens, CD; D016207:Cytokines; D023201:CD40 Ligand