Pulmonary transcriptomic responses indicate a dual role of inflammation in pneumonia development and viral clearance during 2009 pandemic influenza infection

20 p.- 5 fig.- 1 tab.Background: The interaction between influenza virus and the host response to infection clearly plays an important role in determining the outcome of infection. While much is known on the participation of inflammation on the pathogenesis of severe A (H1N1) pandemic 09-influenza virus, its role in the course of non-fatal pneumonia has not been fully addressed.Methods: A systems biology approach was used to define gene expression profiles, histology and viral dynamics in the lungs of healthy immune-competent mice with pneumonia caused by a human influenza A (H1N1) pdm09 virus, which successfully resolved the infection.Results: Viral infection activated a marked pro-inflammatory response at the lung level paralleling the emergence of histological changes. Cellular immune response and cytokine signaling were the two signaling pathway categories more representative of our analysis. This transcriptome response was associated to viral clearance, and its resolution was accompanied by resolution of histopathology.Discussion: These findings suggest a dual role of pulmonary inflammation in viral clearance and development of pneumonia during non-fatal infection caused by the 2009 pandemic influenza virus. Understanding the dynamics of the host's transcriptomic and virological changes over the course of the infection caused by A (H1N1) pdm09 virus may help identifying the immune response profiles associated with an effective response against influenza virus.This work was supported by Instituto de Salud Carlos III: "Programa de Investigacion Comisionada en Gripe (GR09/0021) and Programa para favorecer la incorporacion de grupos de investigacion en las Instituciones del Sistema Nacional de Salud" (EMER07/050). This work was also supported by Biotechnology and Biological Sciences Research Council (BBSRC) grant (BBS/E/I/00002014). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewe