Single-cell spatiotemporal analysis reveals alveolar dendritic cell–T cell immunity hubs defending against pulmonary infection
Abstrak
Abstract 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 + Ido1 + dendritic cells, Cd160 + Cd8 + T cells, and Tnfrsf4 + Cd4 + T cells physiologically co-localize, rapidly expand during SARS-CoV-2 infection, eliminate SARS-CoV-2 with the aid of Slamf9 + 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.
Topik & Kata Kunci
Penulis (29)
Boyi Cong
Xuan Dong
Zongheng Yang
Pin Yu
Yangyang Chai
Jiaqi Liu
Meihan Zhang
Yupeng Zang
Jingmin Kang
Yu Feng
Yi Liu
Weimin Feng
Dehe Wang
Wei Deng
Fengdi Li
Zhiqi Song
Ziqiao Wang
Xiaosu Chen
Hua Qin
Qinyi Yu
Zhiqing Li
Shuxun Liu
Xun Xu
Nanshan Zhong
Xianwen Ren
Chuan Qin
Longqi Liu
Jian Wang
Xuetao Cao
Akses Cepat
- Tahun Terbit
- 2024
- Sumber Database
- DOAJ
- DOI
- 10.1038/s41421-024-00733-5
- Akses
- Open Access ✓