Distinct immunological signatures discriminate severe COVID-19 from non-SARS-CoV-2-driven critical pneumonia
| Autor: | Mirjam Lutz, Ekaterina Friebel, Roland S. Liblau, Antoine Roquilly, Guillaume Martin-Blondel, Manfred Claassen, Benjamin Gaborit, Manuel Kauffmann, Sepideh Babaei, Donatella De Feo, Nicolás Gonzalo Núñez, Nisar P. Malek, Chiara Alberti, Sally Al-Hajj, Susanne Unger, Siri Goepel, Ikram Ayoub, Helene A. Häberle, Jakob Nilsson, Nicole Puertas Jurado, Peter Rosenberger, Stefanie Kreutmair, Sinduya Krishnarajah, Burkhard Becher, Michael Bitzer, Florian Ingelfinger |
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| Přispěvatelé: | Pistre, Karine, Universität Zürich [Zürich] = University of Zurich (UZH), German Cancer Consortium [Heidelberg] (DKTK), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Institute of Experimental Immunology [Zurich], Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, Service d'anesthésie et réanimation chirurgicale [Nantes], Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), German Center for Infectious Research - partner site Tübingen [Tübingen, Allemagne] (DZIF), Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University hospital of Zurich [Zurich], University of Zurich, Becher, Burkhard |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
CD4-Positive T-Lymphocytes Male MESH: CD4-Positive T-Lymphocytes / immunology MESH: Biomarkers / blood [SDV]Life Sciences [q-bio] MESH: HLA Antigens / genetics MESH: COVID-19 / pathology 10263 Institute of Experimental Immunology Hospital-acquired pneumonia Severity of Illness Index 0302 clinical medicine MESH: Pneumonia / immunology HLA Antigens T-Lymphocyte Subsets peptide binding strength Immunopathology Immunology and Allergy MESH: Pneumonia / pathology MESH: T-Lymphocyte Subsets / metabolism COVID high-dimensional single cell analysis Antigen Presentation MESH: Middle Aged spectral flow cytometry immune profiling MESH: SARS-CoV-2 / immunology Middle Aged Acquired immune system MESH: HLA Antigens / immunology 3. Good health [SDV] Life Sciences [q-bio] Infectious Diseases HLA typing 030220 oncology & carcinogenesis MESH: T-Lymphocyte Subsets / immunology 2723 Immunology and Allergy MESH: SARS-CoV-2 / pathogenicity Biomarker (medicine) Cytokines biomarker [SDV.IMM]Life Sciences [q-bio]/Immunology Female MESH: Immunity Innate Angiotensin-Converting Enzyme 2 Adult [SDV.IMM] Life Sciences [q-bio]/Immunology MESH: Immunophenotyping Immunology Antigen presentation 610 Medicine & health Human leukocyte antigen Biology Article 03 medical and health sciences MESH: Natural Killer T-Cells / immunology Immune system immunophenotyping MESH: CD4-Positive T-Lymphocytes / metabolism MESH: Angiotensin-Converting Enzyme 2 / metabolism MESH: Severity of Illness Index medicine Humans 2403 Immunology SARS-CoV-2 COVID-19 GM-CSF 2725 Infectious Diseases Pneumonia biochemical phenomena metabolism and nutrition medicine.disease MESH: COVID-19 / immunology Immunity Innate 030104 developmental biology MESH: Antigen Presentation 10033 Clinic for Immunology 570 Life sciences biology Natural Killer T-Cells Biomarkers |
| Zdroj: | Immunity Immunity, 2021, 54 (7), pp.1578-1593.e5. ⟨10.1016/j.immuni.2021.05.002⟩ |
| ISSN: | 1074-7613 |
| DOI: | 10.1016/j.immuni.2021.05.002 |
| Popis: | Immune profiling of COVID-19 patients has identified numerous alterations in both innate and adaptive immunity. However, whether those changes are specific to SARS-CoV-2 or driven by a general inflammatory response shared across severely ill pneumonia patients remains unknown. Here, we compared the immune profile of severe COVID-19 with non-SARS-CoV-2 pneumonia ICU patients using longitudinal, high-dimensional single-cell spectral cytometry and algorithm-guided analysis. COVID-19 and non-SARS-CoV-2 pneumonia both showed increased emergency myelopoiesis and displayed features of adaptive immune paralysis. However, pathological immune signatures suggestive of T cell exhaustion were exclusive to COVID-19. The integration of single-cell profiling with a predicted binding capacity of SARS-CoV-2-petides to the patients’ HLA profile further linked the COVID-19 immunopathology to impaired virus recognition. Towards clinical translation, circulating NKT cell frequency was identified as a predictive biomarker for patient outcome. Our comparative immune map serves to delineate treatment strategies to interfere with the immunopathologic cascade exclusive to severe COVID-19. Graphical Abstract The pathogen-specific immune alterations in severe COVID-19 remain unknown. Using longitudinal, high-dimensional single-cell spectral cytometry and algorithm-guided comparison of COVID-19 vs. non-SARS-CoV-2-pneumonia patient samples, Kreutmair et al. identify T and NK cell immune signatures specific to SARS-CoV-2. They furthermore reveal NKT cell frequency as a predictive biomarker for COVID-19 outcome prediction and link impaired virus recognition to HLA genetics. |
| Databáze: | OpenAIRE |
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