Seasonal flu kills up to 600,000 people a year worldwide and has a century-old history of pandemics. Some examples include the Spanish flu in the late 1910s or H1N1 in 2009, which together caused more than 50 million lives. “The way we set up the stage tells us that it is not a question of whether, but of when there will be an upcoming pandemic. And preparing for it requires intensive fundamental research and a constant accumulation of knowledge about these viruses and diseases. that cause, ”says Maria João Amorim, IGC principal investigator and leader of the team that conducted the study.

When a virus like grip it enters our lungs, it quickly faces cocktails of molecules that recognize it and alert the host of its presence. The signals go back and activate the file immune response, summoning an army of cells and companions of inflammation. Any exaggeration can destabilize the balance needed to remove the virus and save our tissues from damage. For most people, the clearing comes a few days after infection and leaves very few traces. But for some, flu infection it involves serious complications, resulting from an exacerbated response that damages the lungs.

“We have found that DAF, which means accelerating disintegration factor, aggravates influenza A infection and increases damage to the lungs of mice. This mechanism of influenza virulence and the molecular regulation that underpins it are new to us. “says Amorim. DAF is a receptor that is found on the surface of most cells and works to protect them from being attacked by one of our own immune surveillance systems: the complement. This system protects us against invasive pathogens once it detects them in circulation, inactivating the pathogen itself or within infected cells, mounting a strategy to eliminate them.

“But this can work as a double-edged sword because if the supplement destroys the host cells, there is the associated danger of causing excessive injury by removing too many cells present and inflammation In fact, the severity and mortality of the disease have been associated with the lack or excess of activation of the supplement, which is adjusted by regulators such as DAF, “says Nuno Santos, lead author of the study. Contrary to expectations, the team found that influenza A virus exploits DAF to potentiate complement activation as a mechanism of immune evasion, increasing immune cell recruitment. “By doing so, it can exacerbate the immune response and this is what damages the lungs. Remarkably, this occurs in a way that is independent of the viral load, telling us that it directly affects resistance to infection,” he said. says Zoe Vaz da Silva. , co-author of the study.

The role of DAF in influenza infection may depend on how it interacts with some parts of the virus, causing more or less aggravated responses. “The complement system is important, but not the only component that determines the outcome of infection. These interactions have functional implications and are an unprecedented form of a virus, by altering a host protein from the infected cell, to modulate the immune response. Studying this in the future is crucial, “says Amorim.

This work highlights a new influenza A immune evasion strategy virus and stresses the importance of a balanced immune response to viral infections, which allows the disease to be eliminated without causing harm. Despite its intrinsic protective role, the immune system can be the cause of serious complications during influenza A. infection.

Provided by the Gulbenkian Institute of Science (IGC)