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

Abstract

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.

Keywords

• Influenza
• Mice model
• Inflammation
• Gene expression
• Immune response
• Lung