global transcriptome analysis in influenza-infected mouse lungs reveals the kinetics of innate and adaptive host immune responses全球转录组分析influenza-infected鼠肺显示先天和适应宿主免疫反应的动力学.pdfVIP

Global Transcriptome Analysis in Influenza-Infected Mouse Lungs Reveals the Kinetics of Innate and Adaptive Host Immune Responses 1. 1. 1¤ 1 2 Claudia Pommerenke , Esther Wilk , Barkha Srivastava , Annika Schulze , Natalia Novoselova , 3 1 Robert Geffers , Klaus Schughart * 1 Department of Infection Genetics, Helmholtz Centre for Infection Research and University of Veterinary Medicine Hannover, Braunschweig, Germany, 2 United Institute of Informatics Problems, National Academy of Sciences of Belarus, Minsk, Belarus, 3 Research Group Genome Analytics, Helmholtz Centre for Infection Research, Braunschweig, Germany Abstract An infection represents a highly dynamic process involving complex biological responses of the host at many levels. To describe such processes at a global level, we recorded gene expression changes in mouse lungs after a non-lethal infection with influenza A virus over a period of 60 days. Global analysis of the large data set identified distinct phases of the host response. The increase in interferon genes and up-regulation of a defined NK-specific gene set revealed the initiation of the early innate immune response phase. Subsequently, infiltration and activation of T and B cells could be observed by an augmentation of T and B cell specific signature gene expression. The changes in B cell gene expression and preceding chemokine subsets were associated with the formation of bronchus-associated lymphoid tissue. In addition, we compared the gene expression profiles from wild type mice with Rag2 mutant mice. This analysis readily demonstrated that the deficiency in the T and B cell re