Most people who catch the flu experience a few days of fever, fatigue, and coughing before recovering.
But certain strains of influenza A viruses can cause severe illness, including pneumonia and even acute respiratory failure.
Scientists have long wondered why some strains are so deadly while others cause only mild infections.
A new study from the Paul-Ehrlich-Institut in Germany sheds light on the mystery.
The research, published in Emerging Microbes & Infections, shows that highly pathogenic avian influenza viruses—the kind that occasionally jump from birds to humans—can infect specific immune cells in ways that ordinary flu viruses do not.
This unusual behavior may be what triggers the dangerous “cytokine storms” that make these infections so deadly.
A cytokine storm happens when the immune system overreacts to infection, releasing an overwhelming flood of messenger substances called cytokines. Instead of protecting the body, this overreaction damages tissues and organs, sometimes causing more harm than the virus itself.
The researchers, led by Dr. Martina Anzaghe, studied 11 different strains of influenza A viruses, ranging from common seasonal flu viruses to highly pathogenic avian flu strains.
They looked at how the viruses interacted with different types of human immune cells and how much interferon—a key antiviral signal—was produced.
One surprising finding was that plasmacytoid dendritic cells, a special kind of immune cell, responded strongly to all types of influenza viruses by producing large amounts of interferon-α, regardless of the strain. These cells mount a strong defense without needing to be infected by the virus itself.
But the key difference emerged with other immune cells. The team discovered that highly pathogenic avian influenza viruses could directly infect myeloid dendritic cells and macrophages—two important types of immune cells.
Once infected, these cells produced far more interferon-α than normal. This excess signaling may set off the destructive cascade of inflammation known as a cytokine storm.
“Our results show that not only the usual immune cells we associate with interferon production, but also other types of immune system cells, can determine whether an influenza infection becomes dangerous,” explained Professor Zoe Waibler, acting Vice President of the Paul-Ehrlich-Institut.
This discovery helps explain why avian flu viruses are often so deadly in humans, with much higher mortality rates than seasonal flu. It also underscores the importance of understanding how different viruses interact with the immune system.
By pinpointing which cells are involved in triggering cytokine storms, researchers hope to develop new therapies that can calm excessive immune responses while still allowing the body to fight infection. Such insights may also improve risk assessment for emerging flu strains, helping public health officials prepare for potential outbreaks.
In the long run, this knowledge could make the difference between a severe, life-threatening flu season and a manageable one.
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Source: KSR.
