Natural killer cell immunotypes related to COVID-19 disease severity
Understanding innate immune responses in COVID-19 is important to decipher mechanisms of host responses and interpret disease pathogenesis. Natural killer (NK) cells are innate effector lymphocytes that respond to acute viral infections but might also contribute to immunopathology. Using 28-color fl...
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| Published in | Science immunology Vol. 5; no. 50 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
21.08.2020
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| Subjects | |
| Online Access | Get more information |
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| Abstract | Understanding innate immune responses in COVID-19 is important to decipher mechanisms of host responses and interpret disease pathogenesis. Natural killer (NK) cells are innate effector lymphocytes that respond to acute viral infections but might also contribute to immunopathology. Using 28-color flow cytometry, we here reveal strong NK cell activation across distinct subsets in peripheral blood of COVID-19 patients. This pattern was mirrored in scRNA-seq signatures of NK cells in bronchoalveolar lavage from COVID-19 patients. Unsupervised high-dimensional analysis of peripheral blood NK cells furthermore identified distinct NK cell immunotypes that were linked to disease severity. Hallmarks of these immunotypes were high expression of perforin, NKG2C, and Ksp37, reflecting increased presence of adaptive NK cells in circulation of patients with severe disease. Finally, arming of CD56
NK cells was observed across COVID-19 disease states, driven by a defined protein-protein interaction network of inflammatory soluble factors. This study provides a detailed map of the NK cell activation landscape in COVID-19 disease. |
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| AbstractList | Understanding innate immune responses in COVID-19 is important to decipher mechanisms of host responses and interpret disease pathogenesis. Natural killer (NK) cells are innate effector lymphocytes that respond to acute viral infections but might also contribute to immunopathology. Using 28-color flow cytometry, we here reveal strong NK cell activation across distinct subsets in peripheral blood of COVID-19 patients. This pattern was mirrored in scRNA-seq signatures of NK cells in bronchoalveolar lavage from COVID-19 patients. Unsupervised high-dimensional analysis of peripheral blood NK cells furthermore identified distinct NK cell immunotypes that were linked to disease severity. Hallmarks of these immunotypes were high expression of perforin, NKG2C, and Ksp37, reflecting increased presence of adaptive NK cells in circulation of patients with severe disease. Finally, arming of CD56
NK cells was observed across COVID-19 disease states, driven by a defined protein-protein interaction network of inflammatory soluble factors. This study provides a detailed map of the NK cell activation landscape in COVID-19 disease. |
| Author | Hertwig, Laura Cuapio, Angelica Ljunggren, Hans-Gustaf Aleman, Soo Sandberg, Johan K Reinius, Björn Klingström, Jonas Brownlie, Demi Malmberg, Karl-Johan Cornillet, Martin Buggert, Marcus Strålin, Kristoffer Filipovic, Iva Schaffer, Marie Ask, Eivind Heggernes Eriksson, Lars I Michaëlsson, Jakob Maucourant, Christopher Lentini, Antonio Marquardt, Nicole Folkesson, Elin Björkström, Niklas K Ponzetta, Andrea Hull, Ryan M Haroun-Izquierdo, Alvaro Rooyackers, Olav Strunz, Benedikt Hammer, Quirin |
| Author_xml | – sequence: 1 givenname: Christopher orcidid: 0000-0003-1033-2992 surname: Maucourant fullname: Maucourant, Christopher organization: Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden – sequence: 2 givenname: Iva orcidid: 0000-0002-8166-5500 surname: Filipovic fullname: Filipovic, Iva organization: Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden – sequence: 3 givenname: Andrea orcidid: 0000-0003-3224-802X surname: Ponzetta fullname: Ponzetta, Andrea organization: Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden – sequence: 4 givenname: Soo surname: Aleman fullname: Aleman, Soo organization: Division of Infectious Diseases and Dermatology, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden – sequence: 5 givenname: Martin orcidid: 0000-0001-7981-0927 surname: Cornillet fullname: Cornillet, Martin organization: Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden – sequence: 6 givenname: Laura orcidid: 0000-0002-1170-0948 surname: Hertwig fullname: Hertwig, Laura organization: Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden – sequence: 7 givenname: Benedikt surname: Strunz fullname: Strunz, Benedikt organization: Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden – sequence: 8 givenname: Antonio orcidid: 0000-0003-1239-5495 surname: Lentini fullname: Lentini, Antonio organization: Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden – sequence: 9 givenname: Björn surname: Reinius fullname: Reinius, Björn organization: Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden – sequence: 10 givenname: Demi orcidid: 0000-0001-5932-6425 surname: Brownlie fullname: Brownlie, Demi organization: Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden – sequence: 11 givenname: Angelica surname: Cuapio fullname: Cuapio, Angelica organization: Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden – sequence: 12 givenname: Eivind Heggernes orcidid: 0000-0001-8655-1433 surname: Ask fullname: Ask, Eivind Heggernes organization: The KG Jebsen Center for Cancer Immunotherapy, Institute of Clinical Medicine, University of .Oslo, Oslo, Norway – sequence: 13 givenname: Ryan M orcidid: 0000-0001-7153-4198 surname: Hull fullname: Hull, Ryan M organization: SciLifeLab, Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden – sequence: 14 givenname: Alvaro orcidid: 0000-0003-4557-3606 surname: Haroun-Izquierdo fullname: Haroun-Izquierdo, Alvaro organization: Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden – sequence: 15 givenname: Marie surname: Schaffer fullname: Schaffer, Marie organization: Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden – sequence: 16 givenname: Jonas orcidid: 0000-0001-9076-1441 surname: Klingström fullname: Klingström, Jonas organization: Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden – sequence: 17 givenname: Elin surname: Folkesson fullname: Folkesson, Elin organization: Division of Infectious Diseases, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden – sequence: 18 givenname: Marcus orcidid: 0000-0003-0633-1719 surname: Buggert fullname: Buggert, Marcus organization: Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden – sequence: 19 givenname: Johan K orcidid: 0000-0002-6275-0750 surname: Sandberg fullname: Sandberg, Johan K organization: Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden – sequence: 20 givenname: Lars I surname: Eriksson fullname: Eriksson, Lars I organization: Function Perioperative Medicine and Intensive Care, Karolinska University Hospital, Stockholm, Sweden – sequence: 21 givenname: Olav orcidid: 0000-0002-3391-5448 surname: Rooyackers fullname: Rooyackers, Olav organization: Department Clinical Interventions and Technology CLINTEC, Division for Anesthesiology and Intensive Care, Karolinska Institutet, Stockholm, Sweden – sequence: 22 givenname: Hans-Gustaf surname: Ljunggren fullname: Ljunggren, Hans-Gustaf organization: Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden – sequence: 23 givenname: Karl-Johan surname: Malmberg fullname: Malmberg, Karl-Johan organization: The KG Jebsen Center for Cancer Immunotherapy, Institute of Clinical Medicine, University of .Oslo, Oslo, Norway – sequence: 24 givenname: Jakob surname: Michaëlsson fullname: Michaëlsson, Jakob organization: Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden – sequence: 25 givenname: Nicole orcidid: 0000-0003-3186-4752 surname: Marquardt fullname: Marquardt, Nicole organization: Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden – sequence: 26 givenname: Quirin orcidid: 0000-0003-2968-6061 surname: Hammer fullname: Hammer, Quirin organization: Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden – sequence: 27 givenname: Kristoffer orcidid: 0000-0002-8801-3169 surname: Strålin fullname: Strålin, Kristoffer organization: Division of Infectious Diseases and Dermatology, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden – sequence: 28 givenname: Niklas K orcidid: 0000-0002-0967-076X surname: Björkström fullname: Björkström, Niklas K email: niklas.bjorkstrom@ki.se organization: Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden. niklas.bjorkstrom@ki.se |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/32826343$$D View this record in MEDLINE/PubMed |
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| Contributor | Färnert, Anna Hertwig, Laura Norrby-Teglund, Anna Chen, Puran Dzidic, Majda Wullimann, David Aleman, Soo Butrym, Marta Bergsten, Helena Brighenti, Susanna Chambers, Benedict J Mårtensson, Johan Kvedaraite, Egle Malmberg, Karl-Johan Sönnerborg, Anders Cornillet, Martin Muvva, Jagadeeswara Rao Berglin, Lena Tynell, Janne Michaëlsson, Jakob Loreti, Marco Giulio Marquardt, Nicole Perez-Potti, André Kammann, Tobias Björkström, Niklas K Sohlberg, Ebba Von Kries, Andreas Sandberg, John Tyler Haroun-Izquierdo, Alvaro Lourda, Magdalini Svensson, Mattias Unge, Christian Cuapio, Angelica Flodström-Tullberg, Malin Ljunggren, Hans-Gustaf Varnaite, Renata Sandberg, Johan K Maleki, Kimia T Klingström, Jonas Mjösberg, Jenny Kalsum, Sadaf Brownlie, Demi Glans, Hedvig Ringqvist, Emma Buggert, Marcus Parrot, Tiphaine Strålin, Kristoffer Nauclér, Pontus Rivera-Ballesteros, Olga Eriksson, Lars I Kokkinou, Efthymia Moll, Kirsten Maucourant, Christopher Sekine, Takuya Palma Medina, Laura M Gorin, Jean-Baptiste Gredmark-Russ, Sara Radler, Lena Diaz Lozano, Isabel Akb |
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| Title | Natural killer cell immunotypes related to COVID-19 disease severity |
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