Antigen-Specific Th17 Cells Are Primed by Distinct and Complementary Dendritic Cell Subsets in Oropharyngeal Candidiasis
Antigen-Specific Th17 Cells Are Primed by Distinct and Complementary Dendritic Cell Subsets in Oropharyngeal Candidiasis
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DOI：
10.1371/journal.ppat.1005164
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发表时间：
2015-10-01
期刊：
影响因子：
6.7
通讯作者：
LibundGut-Landmann, Salome
中科院分区：
文献类型：
--
作者：
Trautwein-Weidner, Kerstin;Gladiator, Andre;LibundGut-Landmann, Salome
假丝酵母菌可导致免疫受损个体的严重和慢性皮肤黏膜和全身感染。对黏膜皮肤念珠菌病的保护依赖于T辅助细胞，特别是那些分泌IL-17的细胞。调节T细胞活化和分化以响应真菌在不同组织中侵袭的效应命运的事件知之甚少。在这里，我们产生了一个念珠菌特异的TCR转基因小鼠，对一种新的内源性抗原产生反应，该抗原在包括临床高度相关的白色念珠菌和光滑念珠菌在内的多个遥远的念珠菌物种中保守。用TCR转基因T细胞与口咽念珠菌病(OPC)动物模型相结合，研究了口腔黏膜中不同亚群的树突状细胞(DC)的抗原提呈和Th17免疫反应。念珠菌来源的内源性抗原进入引流淋巴结，并由迁移性DC直接呈递。依赖Flt3L的树突状细胞和依赖CCR2的单核细胞来源的树突状细胞在OPC的抗原提呈和T细胞启动过程中协同工作。相反，朗格汉斯细胞也存在于口腔粘膜中，并已被证明在皮肤中启动Th17细胞，在口服攻击时不需要诱导念珠菌特异性T细胞反应。这突出了不同组织中特定DC亚群的功能区划。这些数据为我们理解组织特异性抗真菌免疫提供了重要的新见解。
Candida spp. can cause severe and chronic mucocutaneous and systemic infections in immunocompromised individuals. Protection from mucocutaneous candidiasis depends on T helper cells, in particular those secreting IL-17. The events regulating T cell activation and differentiation toward effector fates in response to fungal invasion in different tissues are poorly understood. Here we generated a Candida-specific TCR transgenic mouse reactive to a novel endogenous antigen that is conserved in multiple distant species of Candida, including the clinically highly relevant C. albicans and C. glabrata. Using TCR transgenic T cells in combination with an experimental model of oropharyngeal candidiasis (OPC) we investigated antigen presentation and Th17 priming by different subsets of dendritic cells (DCs) present in the infected oral mucosa. Candida-derived endogenous antigen accesses the draining lymph nodes and is directly presented by migratory DCs. Tissue-resident Flt3L-dependent DCs and CCR2-dependent monocyte-derived DCs collaborate in antigen presentation and T cell priming during OPC. In contrast, Langerhans cells, which are also present in the oral mucosa and have been shown to prime Th17 cells in the skin, are not required for induction of the Candida-specific T cell response upon oral challenge. This highlights the functional compartmentalization of specific DC subsets in different tissues. These data provide important new insights to our understanding of tissue-specific antifungal immunity.