Lung cells induce immune response to influenza

Researchers have uncovered some novel and unexpected ways that influenza virus and viral RNA are detected by human lung cells, which may have therapeutic ramifications.

The annual epidemics that threaten between 3 and 5 million people with severe sickness and result in 290,000 to 650,000 fatalities globally are brought on by influenza viruses, which continue to be a serious threat to human health. These viruses can also cause severe symptoms in young, old, and immunocompromised populations.

When these viruses multiply, they predominantly target respiratory epithelial cells, where they harm and kill the cells.

Scientists now understand that these epithelial cells play a crucial role in triggering the immune system's antiviral response and are not just passive barriers that are defenceless against attack.

The team discovered that viral RNA and influenza viruses stimulate two different molecular pathways in which specific proteins set off chain reactions that result in two proteins called “gasdermin D” and “gasdermin E” being processed in such a way that they form membrane pores in the epithelial cells.

These pores allow the release of special agent “cytokines” charged with sparking the immune system into life and also causing the death of the cells which prevents the virus from spreading.

To assess the importance of this finding, the team suppressed the formation of the gasdermin pores to see what would happen, and this resulted in increased replication of influenza viruses, underlining how important these gasdermins are in the antiviral response.

The research has just been published in the journal iScience. Speaking about the research and its implications, Professor Bowie, who is based in Trinity’s Biomedical Sciences Institute, said, “By forming an EU-wide network of scientists with different expertise in immunology and virology, we were able to ask some fundamental questions about how our bodies respond to RNA viruses such as influenza and SARS-CoV-2.

“We realised that very little was known about the initial response to viruses in those early moments when our lungs first encounter a virus. Through Coralie’s work, we were able to make some important discoveries that highlight previously unknown aspects of the immune response to influenza, which we will now build on to examine how relevant they are to other viral infections of the lung, such as SARS-CoV-2 and RSV.”