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 responses in Rag2 mutants could be detected by changes in the global gene expression patterns of the whole lung. In conclusion, our comprehensive gene expression study describes for the first time the entire host response and its kinetics to an acute influenza A infection at the transcriptome level.
Highlights
Influenza A virus has caused major pandemics in recent human history with millions of deaths
Wild type C57BL/6J mice were infected with the mouseadapted influenza A virus PR8 (H1N1) and genome-wide gene expression patterns were analyzed for 60 days post infection (p.i.; Figure 1)
From day 18 to day 60 p.i., minimal changes were observed over time but they still differed from mock-infected controls
Summary
Influenza A virus has caused major pandemics in recent human history with millions of deaths. During an acute virus infection, highly dynamic and interrelated responses are triggered in the host at multiple levels which eventually result in clearance of the pathogen and establishment of a long-lasting immunity. DCs take up antigens by direct infection or phagocytosis of infected dead cells, migrate to the draining lymph nodes where they activate T cells and present pathogen-specific antigens to them (reviewed in [7,10]). This process causes the generation of antigen-specific T cells and the production of neutralizing antibodies (reviewed in [7,10,12,13]). Through the combined action of innate and adaptive immune responses, the infectious pathogen becomes inactivated and cleared from the body, repair processes start to resolve the tissue damages and long-term immunity will be established, including the formation of local bronchusassociated lymphoid tissues (reviewed in [7])
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