Wang Lin, Ma Hui, Wen Zilu, Niu Liangfei, Chen Xinchun, Liu Haiying, Zhang Shulin, Xu Jianqing, Zhu Yijun, Li Hongwei, Chen Hui, Shi Lei, Wan Laiyi, Li Leilei, Li Meiyi, Wong Ka-Wing, Song Yanzheng
Department of Thoracic Surgery, Shanghai Public Health Clinical Center, Shanghai, China.
Department of Scientific Research, Shanghai Public Health Clinical Center, Shanghai, China.
J Infect. 2023 Nov;87(5):373-384. doi: 10.1016/j.jinf.2023.09.004. Epub 2023 Sep 9.
Lung inflammation indicated by 18F-labeled fluorodeoxyglucose (FDG) in patients with tuberculosis is associated with disease severity and relapse risk upon treatment completion. We revealed the heterogeneity and intercellular crosstalk in lung tissues with 18F-FDG avidity and adjacent uninvolved tissues from 6 tuberculosis patients by single-cell RNA-sequencing. Tuberculous lungs had an influx of regulatory T cells (Treg), exhausted CD8 T cells, immunosuppressive myeloid cells, conventional DC, plasmacytoid DC, and neutrophils. Immune cells in inflamed lungs showed general up-regulation of ATP synthesis and interferon-mediated signaling. Immunosuppressive myeloid and Treg cells strongly displayed transcriptions of genes related to tuberculosis disease progression. Intensive crosstalk between IL4I1-expressing myeloid cells and Treg cells involving chemokines, costimulatory molecules, and immune checkpoints, some of which are specific in 18F-FDG-avid lungs, were found. Our analysis provides insights into the transcriptomic heterogeneity and cellular crosstalk in pulmonary tuberculosis and guides unveiling cellular and molecular targets for tuberculosis therapy.
18F标记的氟脱氧葡萄糖（FDG）显示的肺部炎症与肺结核患者的疾病严重程度及治疗结束后的复发风险相关。我们通过单细胞RNA测序揭示了6例肺结核患者中具有18F-FDG亲和力的肺组织及其相邻未受累组织中的异质性和细胞间串扰。结核性肺组织中有调节性T细胞（Treg）、耗竭的CD8 T细胞、免疫抑制性髓样细胞、传统树突状细胞、浆细胞样树突状细胞和中性粒细胞的流入。炎症肺组织中的免疫细胞普遍上调了ATP合成和干扰素介导的信号传导。免疫抑制性髓样细胞和Treg细胞强烈显示出与结核病进展相关基因的转录。发现表达IL4I1的髓样细胞与Treg细胞之间存在涉及趋化因子、共刺激分子和免疫检查点的强烈串扰，其中一些在18F-FDG摄取阳性的肺组织中具有特异性。我们的分析为肺结核的转录组异质性和细胞间串扰提供了见解，并指导揭示结核病治疗的细胞和分子靶点。
