Neurons report infection to the brain

Tired, no appetite, simply sick: whether we have the flu or a nasty rhinovirus, all infections actually have some general symptoms in common. This stereotypical “being sick” is not caused by the infection – rather, the brain actively creates this condition itself when it learns that a virus is up to mischief. As now reported by a working group led by Na-Ryum Bin from Harvard Medical School, there are special nerve cells in the throat that are specifically there to report infections with respiratory tract pathogens to the brain. Her experiments on mice infected with an influenza virus had shown that a special group of sensory nerves triggers the typical general symptoms of the disease, she writes in »Nature«. If you destroy them or turn off a specific receptor on these cells, influenza-infected mice behave as if they were healthy.

When they have the flu, mice are much like us: they eat and drink less, get fevers, and hang around limp. While the feeling of illness generated by the brain itself is uncomfortable, it is an important part of the body’s response to infection. So far, however, it is only partially known how exactly this works. For example in 2022, a research group found a group of neurons in the brain, which makes mice limp and eat and drink less when injected with a bacterial toxin to simulate infection. It is still unclear, for example, how the central nervous system produces fever. And until now it was also unknown exactly how the brain found out regarding the infection.

Many experts suspected, for example, that the immune system functions as a kind of sensory organ and reports infections to the brain through its own signaling substances. Prostaglandin E2 (PGE2), a fat molecule with a hormone function, has long been a hot candidate for such a messenger substance. Many drugs that relieve the feeling of illness inhibit the production of this molecule. According to the idea, this would be produced more strongly in the event of an infection and simply carried with the blood to the brain, where it activates the “disease neurons”. However, that is exactly what does not happen, as Bin’s team demonstrated, among other things. Experiments show that a receptor for prostaglandin E2, known as EP3, is actually decisive for the “being ill” – but switching off the receptor in the brain has no effect on the behavior of the mice.