Every winter, the same scenario repeats itself: runny nose, irritated throat, sticky fatigue that won’t let you go. The common cold, mainly caused by rhinoviruses, is part of the decor. However, behind these little illnesses common at this time of year lies a biological lottery. In some patients, the infection may progress to severe respiratory distress, while in others it may be mild.
A study published on January 19 in Cell Press Blue provides the beginning of an explanation and attempts to paint a picture of the different types of colds. To understand this variability, the team led by Ellen Foxman, professor at Yale University (United States), recreated tiny nose models in the laboratory. These organoids faithfully reproduce the cellular environment of the human nose, the front line against respiratory viruses.
The researchers infected these miniature tissues with a rhinovirus to observe the reaction cell by cell, using single-cell RNA sequencing technology. Result: when the immune response is optimal, the virus only manages to contaminate around 1% of the cells and the infection resolves within a few days. The key to this resistance lies in a family of proteins produced by infected cells: interferons, messengers of immunity, our early warning system.
When scientists artificially block the signal of these interferons, everything changes. More than 30% of cells become infected. Inflammation explodes, cytokines go into overdrive, mucus production intensifies. A molecular conductor, the NF-κB protein, then takes control and triggers an excessive reaction, similar to that observed in vulnerable patients during severe forms.
The war of the mucous membranes
In other words, it’s not just the virus that makes you sick, it’s the quality of the dialogue between our cells and our immune system – so communication is really always the key. Some people have genetic defects that affect the production of interferons, which could explain why a common cold takes them down. Conversely, an overly muscular response can itself become dangerous: the inflammation, then necessary to fight the cold, turns into an uncontrolled fire.
This work raises the question of treatments and their effectiveness depending on the patient. Researchers tested several antivirals, including rupintrivir, an experimental molecule previously abandoned after disappointing clinical trials. In cellular models, this drug manages to calm the immune storm. It could, suggests Live Science, find a second life in patients at risk, particularly those suffering from chronic obstructive pulmonary disease.
A major challenge remains: intervening without completely disarming the immune system. Blocking a central regulator like NF-κB would be like cutting off the electricity to the entire house to turn off a light bulb. The balance to be found is of formidable finesse. Rhinoviruses, champions of rapid mutation, further complicate the situation by quickly developing resistance.
The common cold thus remains a medical paradox: a universal disease, but still poorly understood in its details. These laboratory-developed “artificial noses” do not offer a miracle cure. However, they open a new window on the microwar that takes place in our mucous membranes and remind us that between a simple sniff and hospitalization, everything is sometimes decided on the scale of a handful of molecules.
