Demodex mites modulate sebocyte immune reaction: possible role in the pathogenesis of rosacea

Abstract

BackgroundRosacea is a common facial skin disorder mainly affecting middle-aged adults. Its aetiology is unknown and pathogenesis uncertain. Activation of the host innate immune response has been identified as an important factor. The Demodex mite population in the skin of rosacea patients is significantly higher than in patients with normal skin, suggesting that they may be of aetiological importance in this disorder. ObjectivesTo determine the potential of Demodex mites to interact with the host immune system. MethodsLive Demodex mites were extracted from normal facial skin of control subjects and used in cell stimulation experiments with the immortalized SZ95 sebocyte line. Time- and mite-dose-dependent experiments were performed. Direct effects of Demodex and effects of the medium in which Demodex had been cultured were evaluated on the Toll-like receptor (TLR) signalling pathway on both a gene and protein expression level. ResultsMites modulated TLR signalling events on both mRNA and protein levels in SZ95 sebocytes. An initial trend towards downmodulation of genes in this pathway was observed. A subsequent switch to positive gene upregulation was recorded after 48 h of coculture. Demodex secreted bioactive molecules that affected TLR2 receptor expression by sebocytes. High numbers of Demodex induced proinflammatory cytokine secretion, whereas lower numbers did not. ConclusionsDemodex mites have the capacity to modulate the TLR signalling pathway of an immortalized human sebocyte line. Mites have the capacity to secrete bioactive molecules that affect the immune reactivity of sebocytes. Increasing mite numbers influenced interleukin-8 secretion by these cells. What's already known about this topic? Demodex mites are the largest and most complex organisms of the human facial skin microflora. They are present in the sebaceous follicles of normal skin without eliciting a host immune response. The Demodex folliculorum mite population is markedly increased in the facial skin of patients with rosacea. Activation of the Toll-like receptor (TLR)2 immune response pathway in the skin is an important component of the pathogenesis of rosacea. What does this study add? This study demonstrates that live Demodex mites cocultured with sebocytes have the capacity initially to downregulate their TLR2 response. At a later time point and with increased numbers, Demodex mites activate a TLR2-pathway immune response in these cells. What is the translational message? In low numbers in normal skin, Demodex mites may downregulate the host immune TLR signalling pathway to facilitate their survival. Increased Demodex mite numbers (as seen in patients with rosacea) may trigger a host immune reaction by activation of the TLR2 pathway leading to inflammatory skin changes. Understanding the interaction between these complex organisms and resident skin cells may provide insight into the pathogenesis of rosacea and possibly other skin disorders. Linked Comment:Forton. Br J Dermatol 2018; 179:252-253. Plain language summary available online Respond to this article