Institute of Immunology, Christian-Albrechts Universität zu Kiel and Universitätsklinik Schleswig-Holstein, Kiel, Germany; Institute of Clinical Molecular Biology, Christian-Albrechts Universität zu Kiel, Kiel, Germany.
Department of Cellular Immunology, Clinic for Rheumatology and Clinical Immunology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
Cell. 2019 Mar 7;176(6):1340-1355.e15. doi: 10.1016/j.cell.2019.01.041. Epub 2019 Feb 21.
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 anti-fungal Th17 responses and as a potential risk factor for pulmonary inflammatory diseases.
Th17 细胞在屏障组织中提供保护，但也可能导致免疫病理学。病理性 Th17 反应在人类中的相关性和诱导机制还知之甚少。在这里，我们确定粘膜共生病原体白色念珠菌是人类抗真菌 Th17 细胞的主要直接诱导物。针对其他真菌的 Th17 细胞是通过与白色念珠菌的交叉反应诱导产生的。肠道炎症会扩大白色念珠菌和交叉反应性 Th17 细胞的数量。引人注目的是，对空气中真菌烟曲霉具有交叉反应性的 Th17 细胞会在气道炎症患者中选择性地被激活和扩增，尤其是在急性变应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 反应与由空气传播真菌引起的肺部炎症之间存在直接联系。我们确定对微生物群中单一普遍存在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。
