Transcriptomics in lung tissue upon respiratory syncytial virus infection reveals aging as important modulator of immune activation and matrix maintenance

• Published in: Scientific reports 2018-11, Vol.8 (1), p.16653-13, Article 16653
• Main Authors: Pennings, Jeroen L. A., Mariman, Rob, Hodemaekers, Hennie M., Reemers, Sylvia S. N., Janssen, Riny, Guichelaar, Teun
• Format: Article
• Language: English
• Subjects: 38/39; 38/61; 38/77; 631/250/255/2514; 64/60; 692/308/1426; Aging; Animal tissues; Animals; Antiviral agents; Extracellular matrix; Extracellular Matrix - genetics; Extracellular Matrix - metabolism; Extracellular Matrix - pathology; Female; Gene expression; Gene Expression Profiling; Humanities and Social Sciences; Immune response; Immune system; Infections; Interferon; Lung - immunology; Lung - metabolism; Lung - virology; Lungs; Mice; Mice, Inbred C57BL; multidisciplinary; Respiratory diseases; Respiratory syncytial virus; Respiratory Syncytial Virus Infections - genetics; Respiratory Syncytial Virus Infections - immunology; Respiratory Syncytial Virus Infections - metabolism; Respiratory Syncytial Virus Infections - virology; Respiratory Syncytial Viruses - physiology; Science; Science (multidisciplinary); Signal Transduction; Th1 Cells - immunology; Th1 Cells - metabolism; Transcriptome
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-018-35180-2

Aging poses an increased risk of severe infection by respiratory syncytial virus (RSV). The many different biological pathways comprising the response to infection in lungs that are influenced by aging are complex and remain to be defined more thoroughly. Towards finding new directions in research on aging, we aimed to define biological pathways in the acute response to RSV that are affected in the lungs by aging. We therefore profiled the full transcriptome of lung tissue of mice prior to and during RSV infection both at young and old age. In the absence of RSV, we found aging to downregulate genes that are involved in constitution of the extracellular matrix. Moreover, uninfected old mice showed elevated expression of pathways that resemble injury, metabolic aberrations, and disorders mediated by functions of the immune system that were induced at young age only by an exogenous trigger like RSV. Furthermore, infection by RSV mounted stronger activation of anti-viral type-I interferon pathways at old age. Despite such exaggerated anti-viral responses, old mice showed reduced control of virus. Altogether, our findings emphasize important roles in aging-related susceptibility to respiratory disease for extracellular matrix dysfunctions and dysregulated immune activation in lungs.