TESTING
compared to uncolonized RHE control (Figure 5, red bars). Additionally, in the presence of KTZ, the
overproduction of the two biomarkers was reduced to only a threefold secretion level (Figure 5, red bars), supporting again the use of this antimycotic molecule to reduce the influence of M. furfur on the tissue responses.
Conclusion Organotypic 3D models are nowadays a prerequisite for accelerating our comprehension of skin interactions with its microbiome. In order to accelerate our knowledge on Malassezia overgrowth and provide the community with a tool to evaluate new antimycotic compounds, we presented here the development of a new 3D RHE model mimicking the colonization by M. furfur. Using microbiological, histological,
transcriptomic and immunological assays, we clearly demonstrated that the condition of colonization allows the living yeast to grow and interfere with the epidermal tissue. We illustrated that in our 3D model, M. furfur
invades the upper layers of the reconstructed epidermis with deleterious impacts on the barrier function, inducing an effective immune and inflammatory response, at both gene and protein levels. Indeed, the transcriptomic analysis
revealed that, compared to uncolonized controls, colonized tissues displayed a down- regulation of genes involved in the skin barrier homeostasis, as well as an over-expression of genes playing key roles in the immune response. Moreover, to further attest to the
responsiveness of RHE to M. furfur colonization, we demonstrated that gene expression was consistent with the corresponding protein secretion, as reported by the quantification of IL-8 and HBD-2 proteins by ELISA assays.
HBD-2
53
presented here. This new infectious 3D model and associated efficacy tests are therefore a promising tool to evaluate and promote the entry of new SD and dandruff treatment solutions on the market.
References 1. Borda L, Wikramanayake T. Seborrheic dermatitis and dandruff: a comprehensive review. J. Clin. Investig. Dermatol. 2015 Dec; 3(2): 1-10
IL-8
2. Ranganathan S, Mukhopadhyay T. Dandruff: the most commercially exploited skin disease. Indian J. Dermatol. 2010 Apr-Jun; 55(2): 130- 134
0 2.5 5 7.5 Protein secretion (fold change to control)
Figure 5: Quantification of proteins differentially secreted in the cell culture media of reconstructed human epidermis colonized by Malassezia furfur during three days, in the presence (blue bars) or absence (red bars) of Ketoconazole. Changes in protein secretion are expressed as fold to control (uncolonized reconstructed human epidermis). HBD-2: Human Beta Defensin 2 - IL-8: Interleukin 8
The fact that KTZ treatment moderated the observed impacts of M. furfur on RHE, supports the use of KTZ as an effective antimycotic agent in this model. Altogether, this new 3D microbial skin model and its associated assays are fully adapted to objectivate the efficacy of innovative dermo- cosmetic compounds by two complementary approaches, namely their interaction with the skin in response to infection, as well as their interference with the yeast overgrowth. Efficacy in comparison to KTZ used as a positive reference is possible in the model
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3. Proksch E, Brandner JM, Jensen J-M. The skin: an indispensable barrier. Exp. Derm. 2008; 17: 1063–1072
4. Donnarumma G, Paoletti I, Buommino E, Orlando M, Tufano MA, Baroni A. Malassezia furfur induces the expression of beta- defensin-2 in human keratinocytes in a protein kinase C-dependent manner. Arch. Dermatol. Res. 2004 Apr; 295(11): 474-481
5. Ishibashi Y, Sugita T, Nishikawa A. Cytokine secretion profile of human keratinocytes exposed to Malassezia yeasts. FEMS Immunol. Med. Microbiol. 2006; 48: 400-409
6. Sparber F, Ruchti F, LeibundGut-Landmann S. Host Immunity to Malassezia in Health and Disease. Front. Cell. Infect. Microbiol. 2020. Vol 10 – article 198
7. Choi F, Juhasz M, Atanaskova Mesinkovska N. Topical Ketoconazole: a systematic review of current dermatological applications and future developments. J. Dermatol. Treatment. 2019 30 (8): 760-771
8. Tao R, Wang R, Wan Z, Song Y, Wu Y, Li R. Ketoconazole 2% cream alters the skin fundal microbiome in seborrheic dermatitis: a cohort study. Clin. Exp. Dermatol. 2022 Jun; 47(6): 1088-1096
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November 2022 PERSONAL CARE
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