Human Anti-fungal Th17 Immunity and Pathology Rely on Cross-Reactivity against Candida albicans
Human Anti-fungal Th17 Immunity and Pathology Rely on Cross-Reactivity against Candida albicans
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DOI：
10.1016/j.cell.2019.01.041
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发表时间：
2019-03-07
期刊：
影响因子：
64.5
通讯作者：
Scheffold, Alexander
中科院分区：
文献类型：
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作者：
Bacher, Petra;Hohnstein, Thordis;Scheffold, Alexander
Th17 细胞为屏障组织提供保护，但也可能有助于免疫病理学。人类病理性 Th17 反应的相关性和诱导机制尚不清楚。在这里，我们确定皮肤粘膜致病生物白色念珠菌是人类抗真菌 Th17 细胞的主要直接诱导剂。针对其他真菌的 Th17 细胞是通过与白色念珠菌的交叉反应而诱导的。肠道炎症会增加白色念珠菌和交叉反应性 Th17 细胞的总数。引人注目的是，与空气中的真菌烟曲霉发生交叉反应的 Th17 细胞在气道炎症患者中被选择性激活和扩增，特别是在急性过敏性支气管肺曲霉病期间。这表明针对白色念珠菌的保护性肠道 Th17 反应与空气传播真菌引起的肺部炎症之间存在直接联系。我们确定对单一、普遍存在的微生物群成员的异源免疫是系统性诱导人类抗真菌 Th17 反应的核心机制，也是肺部炎症性疾病的潜在危险因素。
Th17 cells provide protection at barrier tissues but may also contribute to immune pathology. The relevance and induction mechanisms of pathologic Th17 responses in humans are poorly understood. Here, we identify the mucocutaneous pathobiont Candida albicans as the major direct inducer of human anti-fungal Th17 cells. Th17 cells directed against other fungi are induced by cross-reactivity to C. albicans. Intestinal inflammation expands total C. albicans and cross-reactive Th17 cells. Strikingly, Th17 cells cross-reactive to the airborne fungus Aspergillus fumigatus are selectively activated and expanded in patients with airway inflammation, especially during acute allergic bronchopulmonary aspergillosis. This indicates a direct link between protective intestinal Th17 responses against C. albicans and lung inflammation caused by airborne fungi. We identify heterologous immunity to a single, ubiquitous member of the microbiota as a central mechanism for systemic induction of human antifungal Th17 responses and as a potential risk factor for pulmonary inflammatory diseases.