Malassezia globosa Induces Differentiation of Pathogenic Th17 Cells by Inducing IL-23 Secretion by Keratinocytes

IF 3.6 3区生物学 Q2 MYCOLOGY

Mycopathologia Pub Date : 2024-09-16 DOI:10.1007/s11046-024-00890-x

Qiuyu Jia, Jian Hu, Xiaojie Wang, Yuxuan Deng, Jianzhong Zhang, Houmin Li

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Abstract

Malassezia, the most abundant fungal commensal on the mammalian skin, has been linked to several inflammatory skin diseases such as atopic dermatitis, seborrheic dermatitis and psoriasis. This study reveals that epicutaneous application with Malassezia globosa (M. globosa) triggers skin inflammation in mice. RNA-sequencing of the resulting mouse lesions indicates activation of Interleukin-17 (IL-17) signaling and T helper 17 (Th17) cells differentiation pathways by M. globosa. Furthermore, our findings demonstrate a significant upregulation of IL-23, IL-23R, IL-17A, and IL-22 expressions, along with an increase in the proportion of Th17 and pathogenic Th17 cells in mouse skin exposed to M. globosa. In vitro experiments illustrate that M. globosa prompts human primary keratinocytes to secrete IL-23 via TLR2/MyD88/NF-κB signaling. This IL-23 secretion by keratinocytes is shown to be adequate for inducing the differentiation of pathogenic Th17 cells in the skin. Overall, these results underscore the significant role of Malassezia in exacerbating skin inflammation by stimulating IL-23 secretion by keratinocytes and promoting the differentiation of pathogenic Th17 cells.

Graphic Abstract

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球状马拉色菌通过诱导角质形成细胞分泌 IL-23 来诱导致病性 Th17 细胞分化

马拉色菌是哺乳动物皮肤上最丰富的真菌共生菌，与特应性皮炎、脂溢性皮炎和银屑病等多种炎症性皮肤病有关。这项研究揭示了球形马拉色菌（M. globosa）的表皮施用会引发小鼠皮肤炎症。对小鼠皮损进行的 RNA 序列分析表明，球孢子菌激活了白细胞介素-17（IL-17）信号传导和 T 辅助细胞 17（Th17）分化途径。此外，我们的研究结果表明，在暴露于球墨虫的小鼠皮肤中，IL-23、IL-23R、IL-17A和IL-22的表达明显上调，Th17细胞和致病性Th17细胞的比例增加。体外实验表明，球孢子菌通过TLR2/MyD88/NF-κB信号促使人类原发性角朊细胞分泌IL-23。这种由角质形成细胞分泌的 IL-23 被证明足以诱导皮肤中致病性 Th17 细胞的分化。总之，这些结果强调了马拉色菌通过刺激角质形成细胞分泌 IL-23 和促进致病性 Th17 细胞分化而在加剧皮肤炎症中的重要作用。

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来源期刊

Mycopathologia 生物-真菌学

CiteScore

6.80

自引率

3.60%

发文量

审稿时长

3 months

期刊介绍： Mycopathologia is an official journal of the International Union of Microbiological Societies (IUMS). Mycopathologia was founded in 1938 with the mission to ‘diffuse the understanding of fungal diseases in man and animals among mycologists’. Many of the milestones discoveries in the field of medical mycology have been communicated through the pages of this journal. Mycopathologia covers a diverse, interdisciplinary range of topics that is unique in breadth and depth. The journal publishes peer-reviewed, original articles highlighting important developments concerning medically important fungi and fungal diseases. The journal highlights important developments in fungal systematics and taxonomy, laboratory diagnosis of fungal infections, antifungal drugs, clinical presentation and treatment, and epidemiology of fungal diseases globally. Timely opinion articles, mini-reviews, and other communications are usually invited at the discretion of the editorial board. Unique case reports highlighting unprecedented progress in the diagnosis and treatment of fungal infections, are published in every issue of the journal. MycopathologiaIMAGE is another regular feature for a brief clinical report of potential interest to a mixed audience of physicians and laboratory scientists. MycopathologiaGENOME is designed for the rapid publication of new genomes of human and animal pathogenic fungi using a checklist-based, standardized format.