TY - JOUR
T1 - Discriminating mild from critical COVID-19 by innate and adaptive immune single-cell profiling of bronchoalveolar lavages
AU - CONTAGIOUS collaborators
AU - Wauters, Els
AU - Van Mol, Pierre
AU - Garg, Abhishek Dinkarnath
AU - Jansen, Sander
AU - Van Herck, Yannick
AU - Vanderbeke, Lore
AU - Bassez, Ayse
AU - Boeckx, Bram
AU - Malengier-Devlies, Bert
AU - Timmerman, Anna
AU - Van Brussel, Thomas
AU - Van Buyten, Tina
AU - Schepers, Rogier
AU - Heylen, Elisabeth
AU - Dauwe, Dieter
AU - Dooms, Christophe
AU - Gunst, Jan
AU - Hermans, Greet
AU - Meersseman, Philippe
AU - Testelmans, Dries
AU - Yserbyt, Jonas
AU - Tejpar, Sabine
AU - De Wever, Walter
AU - Matthys, Patrick
AU - Neyts, Johan
AU - Wauters, Joost
AU - Qian, Junbin
AU - Lambrechts, Diether
PY - 2021/3
Y1 - 2021/3
N2 - How the innate and adaptive host immune system miscommunicate to worsen COVID-19 immunopathology has not been fully elucidated. Here, we perform single-cell deep-immune profiling of bronchoalveolar lavage (BAL) samples from 5 patients with mild and 26 with critical COVID-19 in comparison to BALs from non-COVID-19 pneumonia and normal lung. We use pseudotime inference to build T-cell and monocyte-to-macrophage trajectories and model gene expression changes along them. In mild COVID-19, CD8+ resident-memory (TRM) and CD4+ T-helper-17 (TH17) cells undergo active (presumably antigen-driven) expansion towards the end of the trajectory, and are characterized by good effector functions, while in critical COVID-19 they remain more naïve. Vice versa, CD4+ T-cells with T-helper-1 characteristics (TH1-like) and CD8+ T-cells expressing exhaustion markers (TEX-like) are enriched halfway their trajectories in mild COVID-19, where they also exhibit good effector functions, while in critical COVID-19 they show evidence of inflammation-associated stress at the end of their trajectories. Monocyte-to-macrophage trajectories show that chronic hyperinflammatory monocytes are enriched in critical COVID-19, while alveolar macrophages, otherwise characterized by anti-inflammatory and antigen-presenting characteristics, are depleted. In critical COVID-19, monocytes contribute to an ATP-purinergic signaling-inflammasome footprint that could enable COVID-19 associated fibrosis and worsen disease-severity. Finally, viral RNA-tracking reveals infected lung epithelial cells, and a significant proportion of neutrophils and macrophages that are involved in viral clearance.
AB - How the innate and adaptive host immune system miscommunicate to worsen COVID-19 immunopathology has not been fully elucidated. Here, we perform single-cell deep-immune profiling of bronchoalveolar lavage (BAL) samples from 5 patients with mild and 26 with critical COVID-19 in comparison to BALs from non-COVID-19 pneumonia and normal lung. We use pseudotime inference to build T-cell and monocyte-to-macrophage trajectories and model gene expression changes along them. In mild COVID-19, CD8+ resident-memory (TRM) and CD4+ T-helper-17 (TH17) cells undergo active (presumably antigen-driven) expansion towards the end of the trajectory, and are characterized by good effector functions, while in critical COVID-19 they remain more naïve. Vice versa, CD4+ T-cells with T-helper-1 characteristics (TH1-like) and CD8+ T-cells expressing exhaustion markers (TEX-like) are enriched halfway their trajectories in mild COVID-19, where they also exhibit good effector functions, while in critical COVID-19 they show evidence of inflammation-associated stress at the end of their trajectories. Monocyte-to-macrophage trajectories show that chronic hyperinflammatory monocytes are enriched in critical COVID-19, while alveolar macrophages, otherwise characterized by anti-inflammatory and antigen-presenting characteristics, are depleted. In critical COVID-19, monocytes contribute to an ATP-purinergic signaling-inflammasome footprint that could enable COVID-19 associated fibrosis and worsen disease-severity. Finally, viral RNA-tracking reveals infected lung epithelial cells, and a significant proportion of neutrophils and macrophages that are involved in viral clearance.
KW - Adaptive Immunity
KW - Bronchoalveolar Lavage
KW - Bronchoalveolar Lavage Fluid
KW - CD4-Positive T-Lymphocytes/cytology
KW - CD8-Positive T-Lymphocytes/cytology
KW - COVID-19/diagnosis
KW - Cell Communication
KW - Gene Expression Profiling
KW - Humans
KW - Immunity, Innate
KW - Lung/virology
KW - Macrophages, Alveolar/cytology
KW - Monocytes/cytology
KW - Neutrophils/cytology
KW - Phenotype
KW - Principal Component Analysis
KW - RNA-Seq
KW - Single-Cell Analysis
KW - Th17 Cells/cytology
U2 - 10.1038/s41422-020-00455-9
DO - 10.1038/s41422-020-00455-9
M3 - Article
C2 - 33473155
SN - 1001-0602
VL - 31
SP - 272
EP - 290
JO - Cell Research (CR)
JF - Cell Research (CR)
IS - 3
ER -