Single-cell spatiotemporal analysis reveals alveolar dendritic cell–T cell immunity hubs defending against pulmonary infection
How immune cells are spatiotemporally coordinated in the lung to effectively monitor, respond to, and resolve infection and inflammation in primed form needs to be fully illustrated. Here we apply immunocartography, a high-resolution technique that integrates spatial and single-cell RNA sequencing (scRNA-seq) through deconvolution and co-localization analyses, to the SARS-CoV-2-infected Syrian hamster model. We generate a comprehensive transcriptome map of the whole process of pulmonary infection from physiological condition, infection initiation, severe pneumonia to natural recovery at organ scale and single-cell resolution, with 142,965 cells and 45 lung lobes from 25 hamsters at 5 time points. Integrative analysis identifies that alveolar dendritic cell-T cell immunity hubs, where Ccr7<sup>+</sup>Ido1<sup>+</sup> dendritic cells, Cd160<sup>+</sup>Cd8<sup>+</sup> T cells, and Tnfrsf4<sup>+</sup>Cd4<sup>+</sup> T cells physiologically co-localize, rapidly expand during SARS-CoV-2 infection, eliminate SARS-CoV-2 with the aid of Slamf9<sup>+</sup> macrophages, and then restore to physiological levels after viral clearance. We verify the presence of these cell subpopulations in the immunity hubs in normal and SARS-CoV-2-infected hACE2 mouse models, as well as in publicly available human scRNA-seq datasets, demonstrating the potential broad relevance of our findings in lung immunity.
Authors
- Shuxun Liu (ORCID: https://orcid.org/0000-0002-6296-7538)
- Qinyi Yu
- Jingmin Kang (ORCID: https://orcid.org/0009-0006-5901-5268)
- Longqi Liu (ORCID: https://orcid.org/0000-0002-5828-5542)
- Xuetao Cao (ORCID: https://orcid.org/0000-0001-9677-7647)
- Yupeng Zang (ORCID: https://orcid.org/0000-0002-5098-1172)
- Boyi Cong
- Zongheng Yang
- Hua Qin
- Xuan Dong (ORCID: https://orcid.org/0000-0003-4740-278X)
- Xianwen Ren (ORCID: https://orcid.org/0000-0002-8558-5401)
- Ziqiao Wang (ORCID: https://orcid.org/0000-0002-6720-4732)
- Xiaosu Chen (ORCID: https://orcid.org/0000-0001-9424-2219)
- Wei Deng (ORCID: https://orcid.org/0000-0002-1619-2313)
- Meihan Zhang
- Yi Liu (ORCID: https://orcid.org/0000-0002-3744-0590)
- Jian Wang (ORCID: https://orcid.org/0000-0002-9482-5227)
- Jiaqi Liu (ORCID: https://orcid.org/0000-0002-9775-2342)
- Xun Xu (ORCID: https://orcid.org/0000-0002-5338-5173)
- Yu Feng (ORCID: https://orcid.org/0009-0008-4746-1070)
- Zhiqing Li (ORCID: https://orcid.org/0000-0003-3208-5726)
- Pin Yü (ORCID: https://orcid.org/0000-0002-8744-1727)
- Yangyang Chai (ORCID: https://orcid.org/0000-0002-3646-7820)
- Dehe Wang (ORCID: https://orcid.org/0000-0002-9465-0957)
- Zhiqi Song (ORCID: https://orcid.org/0000-0001-8628-2309)
- Weimin Feng (ORCID: https://orcid.org/0000-0002-0862-1640)
- Fengdi Li
- Chuan Qin
- Nanshan Zhong (ORCID: https://orcid.org/0009-0008-7677-2572)
Institutions
- BGI Group (China) (CN)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Nankai University (CN)
- Peking Union Medical College Hospital (CN)
- Changchun Observatory (CN)
- Institute of Laboratory Animal Science (CN)
- Zhejiang University (CN)
Publication Details
- Journal
- Cell Discovery
- Published
- 2024-10-16
- DOI
- https://doi.org/10.1038/s41421-024-00733-5
- Citations
- 20
- Primary Topic
- Single-cell and spatial transcriptomics
- Type
- article
- Field-Weighted Citation Impact
- 4.68
Funders
- National Natural Science Foundation of China