Two waves of pro-inflammatory factors are released during the influenza A virus (IAV)-driven pulmonary immunopathogenesis
Two waves of pro-inflammatory factors are released during the influenza A virus (IAV)-driven pulmonary immunopathogenesis
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甲型流感病毒 (IAV) 驱动的肺部免疫发病过程中释放两波促炎因子
DOI：
10.1371/journal.ppat.1008334
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发表时间：
2020-02
期刊：
影响因子：
6.7
通讯作者：
Zhang Hui
中科院分区：
文献类型：
--
作者：
Zhang Junsong;Liu Jun;Yuan Yaochang;Huang Feng;Ma Rong;Luo Baohong;Xi Zhihui;Pan Ting;Liu Bingfeng;Zhang Yiwen;Zhang Xu;Luo Yuewen;Wang Jin;Zhao Meng;Lu Gen;Deng Kai;Zhang Hui
甲型流感病毒（IAV）感染是一个复杂的过程。 IAV 扩散到肺部后，会释放大量促炎细胞因子和趋化因子，这在很大程度上决定了感染的结果。利用单细胞RNA测序（scRNA-seq）分析，我们系统地、连续地分析了感染小鼠肺组织中超过16,000个免疫细胞的转录组，并证明了两波促炎因子的释放。一组 IAV 感染的 PD-L1+ 中性粒细胞是早期阶段（感染后 1-3 天）第一波的主要贡献者。值得注意的是，在后期（感染后第7天），当免疫细胞中几乎检测不到IAV时，一组血小板因子4阳性（Pf4+）巨噬细胞产生了另一波促炎因子，这些因子可能是肺泡巨噬细胞（AM）的前体。此外，单细胞信号传导图识别了不同簇之间的谱系间串扰，有助于更好地理解 PD-L1+ 中性粒细胞和 Pf4+-巨噬细胞的特征。我们的数据特征性地阐明了免疫发病机制发展过程中浸润的免疫细胞及其促炎因子的产生，并破译了 IAV 驱动的肺部炎症反应的重要机制。
Influenza A virus (IAV) infection is a complicated process. After IAVs spread to the lung, extensive pro-inflammatory cytokines and chemokines are released, which largely determine the outcome of infection. Using a single-cell RNA sequencing (scRNA-seq) assay, we systematically and sequentially analyzed the transcriptome of more than 16,000 immune cells in the pulmonary tissue of infected mice, and demonstrated that two waves of pro-inflammatory factors were released. A group of IAV-infected PD-L1+ neutrophils were the major contributor to the first wave at an earlier stage (day 1–3 post infection). Notably, at a later stage (day 7 post infection) when IAV was hardly detected in the immune cells, a group of platelet factor 4-positive (Pf4+)-macrophages generated another wave of pro-inflammatory factors, which were probably the precursors of alveolar macrophages (AMs). Furthermore, single-cell signaling map identified inter-lineage crosstalk between different clusters and helped better understand the signature of PD-L1+ neutrophils and Pf4+-macrophages. Our data characteristically clarified the infiltrated immune cells and their production of pro-inflammatory factors during the immunopathogenesis development, and deciphered the important mechanisms underlying IAV-driven inflammatory reactions in the lung.
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DOI：
10.1038/nri3665
发表时间：
2014-05
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1126/science.1247651
发表时间：
2014-02-14
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Jaitin DA;Kenigsberg E;Keren-Shaul H;Elefant N;Paul F;Zaretsky I;Mildner A;Cohen N;Jung S;Tanay A;Amit I
通讯作者：
Amit I
DOI：
10.4337/9781783474684.00062
发表时间：
2019
期刊：
Concepts for International Law
影响因子：
--
作者：
Mario Prost
通讯作者：
Mario Prost
影响因子：
64.8
作者：
Wallrapp A;Riesenfeld SJ;Burkett PR;Abdulnour RE;Nyman J;Dionne D;Hofree M;Cuoco MS;Rodman C;Farouq D;Haas BJ;Tickle TL;Trombetta JJ;Baral P;Klose CSN;Mahlakõiv T;Artis D;Rozenblatt-Rosen O;Chiu IM;Levy BD;Kowalczyk MS;Regev A;Kuchroo VK
通讯作者：
Kuchroo VK
影响因子：
9.3
作者：
Steuerman Y;Cohen M;Peshes-Yaloz N;Valadarsky L;Cohn O;David E;Frishberg A;Mayo L;Bacharach E;Amit I;Gat-Viks I
通讯作者：
Gat-Viks I