%0 Journal Article
%T Two waves of pro-inflammatory factors are released during the influenza A virus (IAV)-driven pulmonary immunopathogenesis
%A Baohong Luo
%A Bingfeng Liu
%A Feng Huang
%A Gen Lu
%A Hui Zhang
%A Jin Wang
%A Jun Liu
%A Junsong Zhang
%A Kai Deng
%A Meng Zhao
%A Rong Ma
%A Ting Pan
%A Xu Zhang
%A Yaochang Yuan
%A Yiwen Zhang
%A Yuewen Luo
%A Zhihui Xi
%J -
%D 2020
%R 10.1371/journal.ppat.1008334
%X 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¨C3 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
%K Influenza A virus
%K Neutrophils
%K Viral gene expression
%K Immune cells
%K Macrophages
%K Inflammation
%K Cytokines
%K Influenza viruses
%U https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1008334