Introduction Malassezia furfur, a dimorphic, lipid-dependent fungal species, is present as part of the normal cutaneous flora but can cause a wide range of cutaneous inflammatory diseases and even systemic infectious diseases. Several inflammatory skin diseases are directly associated with M. furfur including tinea versicolor and Malassezia folliculitis. In addition, atopic dermatitis, seborrheic dermatitis (dandruff), and psoriasis are conditions aggravated by the presence of M. furfur.
Hypothesis Toll-like receptors, part or the innate immune system, are capable of recognizing various molecules on pathogens to activate the inflammatory response. We hypothesize that the lipid rich cell wall of M. furfur inhibits inflammation by blocking the Toll-like receptor (TLR) pathway.
Methods M. furfur CBS 1878 was cultivated on the modified Leeming-Notman media at 34°C for 4 days and prepared by probe sonication. The level of endotoxin contaminating the M. furfur was quantified with a Limulus Amoebocyte Lysate assay and found to be ≤0.1 ng/ml. Chloroform/methanol method was used to extract lipid from whole yeast cells. We compared the immunomodulatory capacity of normal Malassezia furfur (MF), lipid extract from MF (lipid), and lipid-depleted MF [MF(-L)]. Healthy human peripheral blood mononuclear cells were stimulated with LPS derived from Salmonella typhosa, 19-kDa lipoprotein of Mycobacterium tuberculosis, Propionibacterium acnes, and M. furfur. The amounts of TNF-α, IL-6 and IL-1β were measured by ELISA. TLR2 cell-surface expression was examined by flow cytometry and mRNA levels observed by quantitative polymerase chain reaction (qPCR).
Results Spores of M. furfur induce minimal inflammatory response in peripheral blood monocytes. The lipid-depleted M. furfur induces a significant inflammatory response which is at least partly TLR2 dependent. The cell wall lipid of M. furfur inhibits cytokine production in monocytes induced by 19kD, a TLR2 ligand. The cell wall lipid of M. furfur downregulates TLR2 mRNA and protein expression.
Conclusion In summary, the cell wall lipid from M. furfur inhibits the inflammatory response in monocytes via TLR2 downregulation and thus may play a role in modulating the immune response in cutaneous inflammatory disorders.
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