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Natural killer cell activation related to clinical outcome of COVID-19

Natural killer cell activation related to clinical outcome of COVID-19

来源:medRxiv_logomedRxiv
英文摘要

Understanding innate immune responses in COVID-19 is important for deciphering mechanisms of host responses and interpreting disease pathogenesis. Natural killer (NK) cells are innate effector lymphocytes that respond to acute viral infections, but might also contribute to immune pathology. Here, using 28-color flow cytometry, we describe a state of strong NK cell activation across distinct subsets in peripheral blood of COVID-19 patients, a pattern mirrored in scRNA-seq signatures of lung NK cells. Unsupervised high-dimensional analysis identified distinct immunophenotypes that were linked to disease severity. Hallmarks of these immunophenotypes were high expression of perforin, NKG2C, and Ksp37, reflecting a high presence of adaptive NK cell expansions in circulation of patients with severe disease. Finally, arming of CD56bright NK cells was observed in course of COVID-19 disease states, driven by a defined protein-protein interaction network of inflammatory soluble factors. This provides a detailed map of the NK cell activation-landscape in COVID-19 disease.

Reinius Bj?rn、Haroun-Izquierdo Alvaro、Schaffer Marie、Klingstr?m Jonas、Rooyackers Olav、Hammer Quirin、Str?lin Kristoffer、Karolinska COVID-19 Study Group、Aleman Soo、Lentini Antonio、Brownlie Demi、Hull Ryan M.、Bj?rkstr?m Niklas K.、Eriksson Lars I.、Hertwig Laura、Maucourant Christopher、Marquardt Nicole、Filipovic Iva、Strunz Benedikt、Ponzetta Andrea、Malmberg Karl-Johan、Cornillet Martin、Ask Eivind Heggernes、Folkesson Elin、Buggert Marcus、Ljunggren Hans-Gustaf、Micha?lsson Jakob、Gomez Angelica Cuapio、Sandberg Johan K.

Department of Medical Biochemistry and Biophysics, Karolinska InstitutetCenter for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University HospitalCenter for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University HospitalCenter for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University HospitalDepartment Clinical Interventions and Technology CLINTEC, Division for Anesthesiology and Intensive Care, Karolinska Institutet||Function Perioperative Medicine and Intensive Care, Karolinska University HospitalCenter for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University HospitalDepartment of Infectious Diseases, Karolinska University HospitalDepartment of Infectious Diseases, Karolinska University HospitalDepartment of Medical Biochemistry and Biophysics, Karolinska InstitutetCenter for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University HospitalSciLifeLab, Department of Microbiology, Tumor and Cell Biology, Karolinska InstitutetCenter for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University HospitalDepartment of Physiology and Pharmacology, Section for Anesthesiology and Intensive Care, Karolinska Institutet||Function Perioperative Medicine and Intensive Care, Karolinska University HospitalCenter for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University HospitalCenter for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University HospitalCenter for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University HospitalCenter for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University HospitalCenter for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University HospitalCenter for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University HospitalCenter for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital||Department of Medical Biochemistry and Biophysics, Karolinska Institutet||The KG Jebsen Center for Cancer Immunotherapy, Institute of Clinical Medicine, University of OsloCenter for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University HospitalDepartment of Cancer Immunology, Institute for Cancer Research, Oslo University HospitalDepartment of Infectious Diseases, Karolinska University HospitalCenter for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University HospitalCenter for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University HospitalCenter for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University HospitalCenter for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University HospitalCenter for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital

10.1101/2020.07.07.20148478

基础医学

Reinius Bj?rn,Haroun-Izquierdo Alvaro,Schaffer Marie,Klingstr?m Jonas,Rooyackers Olav,Hammer Quirin,Str?lin Kristoffer,Karolinska COVID-19 Study Group,Aleman Soo,Lentini Antonio,Brownlie Demi,Hull Ryan M.,Bj?rkstr?m Niklas K.,Eriksson Lars I.,Hertwig Laura,Maucourant Christopher,Marquardt Nicole,Filipovic Iva,Strunz Benedikt,Ponzetta Andrea,Malmberg Karl-Johan,Cornillet Martin,Ask Eivind Heggernes,Folkesson Elin,Buggert Marcus,Ljunggren Hans-Gustaf,Micha?lsson Jakob,Gomez Angelica Cuapio,Sandberg Johan K..Natural killer cell activation related to clinical outcome of COVID-19[EB/OL].(2025-03-28)[2025-08-08].https://www.medrxiv.org/content/10.1101/2020.07.07.20148478.点此复制

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