NK cell receptor and ligand composition influences the clearance of SARS-CoV-2
Journal
The Journal of Clinical Investigation
Journal Volume
131
Journal Issue
21
Date Issued
2021
Author(s)
Hsieh, Wan-Chen
Lai, En-Yu
Liu, Yu-Ting
Wang, Yi-Fu
Tzeng, Yi-Shiuan
Cui, Lu
Lai, Yun-Ju
Huang, Hsiang-Chi
Huang, Jia-Hsin
Ni, Hung-Chih
Tsai, Dong-Yan
Liang, Jian-Jong
Liao, Chun-Che
Lu, Ya-Ting
Jiang, Laurence
Liu, Ming-Tsan
Chen, Chung-Yu
Chang, Yao-Ming
Wernig, Gerlinde
Li, Chia-Wei
Lin, Kuo-I
Lin, Yi-Ling
Tsai, Huai-Kuang
Huang, Yen-Tsung
Chen, Shih-Yu
Abstract
To explore how the immune system controls clearance of SARS-CoV-2, we used a single-cell, mass cytometry-based proteomics platform to profile the immune systems of 21 patients who had recovered from SARS-CoV-2 infection without need for admission to an intensive care unit or for mechanical ventilation. We focused on receptors involved in interactions between immune cells and virus-infected cells. We found that the diversity of receptor repertoires on natural killer (NK) cells was negatively correlated with the viral clearance rate. In addition, NK subsets expressing the receptor DNAM1 were increased in patients who more rapidly recovered from infection. Ex vivo functional studies revealed that NK subpopulations with high DNAM1 expression had cytolytic activities in response to target cell stimulation. We also found that SARS-CoV-2 infection induced the expression of CD155 and nectin-4, ligands of DNAM1 and its paired coinhibitory receptor TIGIT, which counterbalanced the cytolytic activities of NK cells. Collectively, our results link the cytolytic immune responses of NK cells to the clearance of SARS-CoV-2 and show that the DNAM1 pathway modulates host-pathogen interactions during SARS-CoV-2 infection.
Subjects
COVID-19; NK cells
SDGs
Other Subjects
natural killer cell receptor; nectin; CD226 antigen; cell adhesion molecule; immunoglobulin receptor; ligand; natural killer cell lectin like receptor subfamily D; natural killer cell receptor; nectin4 protein, human; poliovirus receptor; T lymphocyte antigen; TIGIT protein, human; virus receptor; adult; aged; Article; artificial ventilation; clinical article; controlled study; coronavirus disease 2019; cytolysis; ex vivo study; female; HEK293T cell line; human; human cell; human tissue; LCL 721.221 cell line; male; mass cytometry; natural killer cell; natural killer cell mediated cytotoxicity; peripheral blood mononuclear cell; protein expression; protein expression level; proteomics; Severe acute respiratory syndrome coronavirus 2; target cell; viral clearance; virus immunity; adolescent; animal; cohort analysis; cytotoxicity; immunology; immunophenotyping; in vitro study; middle aged; mouse; pandemic; SCID mouse; virology; virus load; xenograft; young adult; Adolescent; Adult; Aged; Animals; Antigens, Differentiation, T-Lymphocyte; Cell Adhesion Molecules; Cohort Studies; COVID-19; Cytotoxicity, Immunologic; Female; Heterografts; Host Microbial Interactions; Humans; Immunophenotyping; In Vitro Techniques; Killer Cells, Natural; Ligands; Male; Mice; Mice, SCID; Middle Aged; NK Cell Lectin-Like Receptor Subfamily D; Pandemics; Receptors, Immunologic; Receptors, Natural Killer Cell; Receptors, Virus; SARS-CoV-2; Viral Load; Young Adult
Publisher
AMER SOC CLINICAL INVESTIGATION INC
Type
journal article