The Skin Commensal Yeast Malassezia Triggers a Type 17 Response that Coordinates Anti-fungal Immunity and Exacerbates Skin Inflammation
The Skin Commensal Yeast Malassezia Triggers a Type 17 Response that Coordinates Anti-fungal Immunity and Exacerbates Skin Inflammation
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DOI：
10.1016/j.chom.2019.02.002
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发表时间：
2019-03-13
影响因子：
30.3
通讯作者：
LeibundGut-Landmann, Salome
中科院分区：
文献类型：
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作者：
Sparber, Florian;De Gregorio, Corinne;LeibundGut-Landmann, Salome
哺乳动物皮肤的共生真菌，例如马拉色菌属的真菌，与特应性皮炎和其他常见的炎症性皮肤病有关。对真菌共生与疾病表现之间因果关系的理解仍然不完整。通过开发小鼠表皮感染模型，我们发现了马拉色菌属。选择性诱导IL-17和相关细胞因子。这种反应是防止皮肤真菌过度生长的关键，因为 IL-23-IL-17 轴的破坏会损害马拉色菌特异性的皮肤免疫力。在皮肤完整性受损的情况下，类似于特应性皮炎的标志，马拉色菌的存在会显着加剧皮肤炎症，这又是 IL-23 和 IL-17 依赖性的。一致地，我们发现健康个体和特应性皮炎患者中记忆 T 细胞的 CCR6(+) Th17 子集是马拉色菌特异性的，因此后者显示出这些细胞的频率增加。因此，马拉色菌诱导的 17 型反应对于协调抗真菌免疫和积极促进皮肤炎症至关重要。
Commensal fungi of the mammalian skin, such as those of the genus Malassezia, are associated with atopic dermatitis and other common inflammatory skin disorders. Understanding of the causative relationship between fungal commensalism and disease manifestation remains incomplete. By developing a murine epicutaneous infection model, we found Malassezia spp. selectively induce IL-17 and related cytokines. This response is key in preventing fungal overgrowth on the skin, as disruption of the IL-23-IL-17 axis compromises Malassezia-specific cutaneous immunity. Under conditions of impaired skin integrity, mimicking a hallmark of atopic dermatitis, the presence of Malassezia dramatically aggravates cutaneous inflammation, which again was IL-23 and IL-17 dependent. Consistently, we found a CCR6(+) Th17 subset of memory T cells to be Malassezia specific in both healthy individuals and atopic dermatitis patients, whereby the latter showed enhanced frequency of these cells. Thus, the Malassezia-induced type 17 response is pivotal in orchestrating antifungal immunity and in actively promoting skin inflammation.