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Cell. 2019 Mar 7;176(6):1340-1355.e15. doi: 10.1016/j.cell.2019.01.041. Epub 2019 Feb 21.

Human Anti-fungal Th17 Immunity and Pathology Rely on Cross-Reactivity against Candida albicans.

Author information

1
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.
2
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.
3
Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology-Hans Knoell Institute (HKI), Jena, Germany.
4
Department of Pediatric Pulmonology, Immunology and Intensive Care Medicine, Cystic Fibrosis Centre Berlin, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
5
Robert Koch Institute Berlin, FG16 Berlin, Germany.
6
Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany.
7
Center for Translational Medicine-Medical Clinic I, Marien Hospital Herne-University Hospital of the Ruhr-University Bochum, Herne, Germany; Berlin-Brandenburg Center for Regenerative Therapies, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
8
Institute for Medical Immunology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
9
Miltenyi Biotec GmbH, Bergisch Gladbach, Germany.
10
Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Department I of Internal Medicine, Clinical Trials Centre Cologne (ZKS Köln), German Centre for Infection Research (DZIF) partner site Bonn-Cologne, Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany.
11
Labor Dr. Wisplinghoff, Institute for Virology and Microbiology, Witten/Herdecke University, Witten, Germany; Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Cologne, Germany.
12
Department of Dermatology and Allergy, Division of Allergy and Immunology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
13
Department of Gastroenterology, Rheumatology and Infectious Diseases, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
14
Department of Gastroenterology, Rheumatology and Infectious Diseases, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany; Gastroenterologie am Bayerischen Platz, Berlin, Germany.
15
Department of Infectious Diseases and Respiratory Medicine, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
16
Department of Infectious Diseases and Respiratory Medicine, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany; Division of Pulmonary Inflammation, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
17
Department of Infectious Diseases and Respiratory Medicine, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany; German Center for Lung Research (DZL), Berlin, Germany.
18
Department of Cardiothoracic and Vascular Surgery, German Heart Center Berlin, Germany; DZHK (German Centre for Cardiovascular Research), partner site Berlin, Berlin, Germany.
19
Department of Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology-Hans Knoell Institute (HKI), Jena, Germany.
20
Department of Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology-Hans Knoell Institute (HKI), Jena, Germany; Institute of Microbiology, Friedrich Schiller University, Jena, Germany.
21
Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology-Hans Knoell Institute (HKI), Jena, Germany; Institute of Microbiology, Friedrich Schiller University, Jena, Germany.
22
Institute of Immunology, Christian-Albrechts Universität zu Kiel and Universitätsklinik Schleswig-Holstein, Kiel, Germany. Electronic address: alexander.scheffold@uksh.de.

Abstract

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.

KEYWORDS:

Aspergillus fumigatus; Candida albicans; T cell cross-reactivity; Th17; airway inflammation; allergic bronchopulmonary aspergillosis (ABPA); anti-fungal immunity; antigen-reactive T cell enrichment (ARTE); cystic fibrosis; heterologous immunity; microbiota

PMID:
30799037
DOI:
10.1016/j.cell.2019.01.041

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