Feeling Anti-Social When You’re Sick? Signals to the Brain Are Responsible
Why does being sick make us want to skip projects? It’s a familiar change: Before a sore throat or fatigue sets in, the motivation to see people often fades. This early withdrawal is not just due to mood or fatigue: in many species it is one of the clearest signs that the body has already detected an infection.
A new study in Cell begins to explain why. Scientists at MIT’s Picower Institute for Learning and Memory attributed this social withdrawal to a surprisingly specific interaction between the immune system and the brain. A single inflammatory molecule, encountering its corresponding receptor on a group of neurons, seems to set in motion a dedicated “not tonight” pathway.
This discovery offers one of the clearest looks at how illness shapes behavior, not as a side effect of feeling unwell, but as an active process embedded in the brain’s circuits.
“Our results show that social isolation following an immune challenge is self-imposed and driven by an active neural process, rather than a secondary consequence of physiological symptoms of illness, such as lethargy,” said Gloria Choi, co-senior author of the study, in a press release.
How immune signals trigger social withdrawal
To understand what triggers this early social withdrawal, researchers began by studying the immune system’s own signaling molecules. When the body detects an infection, it releases chemical messengers called cytokines. The team wondered whether any of these molecules could also send instructions to the brain.
Research shows that neuronal activation was significantly greater as measured with fos (magenta) when IL-1 beta was administered compared to when a control chemical (vehicle) was administered.
(Image credit: Cho Lab/MIT Picower Institute)
They tested them one at a time. By injecting 21 different cytokines into the brains of mice, they looked for anything that mimicked the same social decline seen during the disease. Only interleukin-1 beta, or IL-1β – a molecule linked to inflammation – produced a complete behavioral change.
From there, they investigated where IL-1β might be acting in the brain. The molecule can only work when it binds to its corresponding receptor, called IL-1R1. This research led to the dorsal raphe nucleus (DRN), a region involved in social behavior and home to many serotonin-producing neurons.
Learn more: Mood swings during illness are caused by complex brain-immune crosstalk
The brain circuit that disables social behavior
With the identified DRN as a starting point, the team traced what these IL-1β-sensitive neurons do. Many release serotonin, a chemical linked to mood and social motivation – a clue that this pathway could influence more than just fatigue.
When researchers activated these neurons in healthy mice, the animals became socially disengaged. Silencing the same neurons had the opposite result: the sick mice stopped avoiding others, even though they still felt lazy. This division suggests that fatigue and social withdrawal come from two different biological systems and not just one.
Next, the researchers looked at where these cells send their signals. Multiple downstream regions were linked to social behavior, but only one pathway replicated the full effect. Using optogenetics – a technique that turns neurons on or off with pulses of light – the team activated the connection between the DRN and the intermediate lateral septum, a region involved in social processing. The mice behaved as if they were instantly sick.
The same circuit was activated when the animals were confronted with a real salmonella infection, reinforcing the hypothesis that this mechanism plays out in a natural disease.
Big questions about disease and the brain
The study maps a pathway linking an immune signal to a neural circuit that drives social withdrawal, but the results also leave several open questions.
It remains unclear whether IL-1R1-expressing neurons contribute to other pathological behaviors, or whether the serotonin produced by many of these cells plays a direct role in the response.
Learn more: Why do I get sick so often, while others stay in strangely good health?
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