Toll-like receptor 2 (TLR2) mediates intracellular signalling in human keratinocytes in response to Malassezia furfur.
Toll-like receptors (TLRs) are crucial players in the innate immune response to microbial invaders. The lipophilic yeast Malassezia furfur has been implicated in the triggering of scalp lesions in psoriasis. The aim of the present study was to assess the role of TLRs in the defence against M. furfur infection. The expression of the myeloid differentiation factor 88 (MyD88) gene, which is involved in the signalling pathway of many TLRs, was also analysed. In addition, a possible correlation of antimicrobial peptides of the beta-defensin family to TLRs was tested. Human keratinocytes infected with M. furfur and a variety of M. furfur-positive psoriatic skin biopsies were analysed by RT-PCR, for TLRs, MyD88, human beta-defensin 2 (HBD-2), HBD-3 and interleukin-8 (IL-8) mRNA expression. When keratinocytes were infected with M. furfur, an up-regulation for TLR2, MyD88, HBD-2, HBD-3 and IL-8 mRNA was demonstrated, compared to the untreated cells. The same results were obtained when psoriatic skin biopsies were analysed. The M. furfur-induced increase in HBD-2 and IL-8 gene expression is inhibited by anti-TLR2 neutralising antibodies, suggesting that TLR2 is involved in the M. furfur-induced expression of these molecules. These findings suggest the importance of TLRs in skin protection against fungi and the importance of keratinocytes as a component of innate immunity.
Baroni
Adone
A
Department of Dermatology, Faculty of Medicine and Surgery, Second University of Naples, Naples, Italy.
Orlando
Manuela
M
Donnarumma
Giovanna
G
Farro
Pietro
P
Iovene
Maria Rosaria
MR
Tufano
Maria Antonietta
MA
Buommino
Elisabetta
E
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000502:physiology; D001706:Biopsy; D049109:Cell Proliferation; D002478:Cells, Cultured; D003881:Dermatomycoses / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D005786:Gene Expression Regulation; D006801:Humans; D016209:Interleukin-8 / Q000032:analysis / Q000235:genetics / Q000502:physiology; D015603:Keratinocytes / Q000737:chemistry / Q000382:microbiology* / Q000473:pathology / Q000502:physiology*; D008290:Malassezia / Q000502:physiology*; D053594:Myeloid Differentiation Factor 88; D011565:Psoriasis / Q000382:microbiology / Q000473:pathology / Q000503:physiopathology; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D012867:Skin / Q000737:chemistry / Q000382:microbiology / Q000473:pathology; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000502:physiology*; D023083:beta-Defensins / Q000235:genetics / Q000502:physiology
D048868:Adaptor Proteins, Signal Transducing; C106641:DEFB4A protein, human; D016209:Interleukin-8; C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; D012333:RNA, Messenger; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D023083:beta-Defensins