期刊
CELL RESEARCH
卷 31, 期 3, 页码 272-290出版社
SPRINGERNATURE
DOI: 10.1038/s41422-020-00455-9
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资金
- KULeuven (Belgium)
- UZLeuven (Belgium)
- Grand Challenges Program of VIB
- Flemish Government [VR 2016 2312 Doc.1521/4]
- KU Leuven M.D. Davidse Research Chair for Immuno-oncological Research
- Research Foundation Flanders (FWO) [G0B4620N]
- KU Leuven [C14/19/098, POR/16/040]
- Kom op Tegen Kanker [KOTK/2018/11509/1]
- FWO PhD fellowship [1S66020N, 11E9819N]
- Stichting tegen Kanker (Mandate for basic & clinical oncology research)
- FWO Fundamental Clinical Mandate [1833317N]
- Research Foundation Flanders (FWO) (EOS grant) [30837538]
Single-cell deep-immune profiling revealed that specific T cells in mild COVID-19 patients exhibit active expansion and function, while in critical COVID-19 they remain more naive. Furthermore, the monocyte-to-macrophage trajectories show enrichment of chronic hyperinflammatory monocytes and depletion of anti-inflammatory alveolar macrophages in critical COVID-19.
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 (T-RM) and CD4(+) T-helper-17 (T-H17) 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 naive. Vice versa, CD4(+) T-cells with T-helper-1 characteristics (T-H1-like) and CD8(+) T-cells expressing exhaustion markers (T-EX-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.
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