Feeling Anti-Social When You’re Sick? Signals to the Brain Are Responsible
Why does being sick make us want to skip plans? It’s a familiar shift: before the sore throat or fatigue sets in, the motivation to see people often fades. That early pullback isn’t just mood or tiredness — across many species, it’s 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 have traced this social retreat to a surprisingly specific interaction between the immune system and the brain. A single inflammatory molecule, meeting its matching receptor on a cluster of neurons, appears to set a dedicated “not tonight” pathway into motion.
The discovery offers one of the clearest looks at how sickness shapes behavior, not as a side effect of feeling awful, but as an active process built into the brain’s circuitry.
“Our findings show that social isolation following immune challenge is self-imposed and driven by an active neural process, rather than a secondary consequence of physiological symptoms of sickness, such as lethargy,” said study co-senior author, Gloria Choi, in a press release.
How Immune Signals Trigger Social Withdrawal
To understand what triggers this early social pullback, the researchers began with the immune system’s own signaling molecules. When the body detects infection, it releases chemical messengers called cytokines. The team wondered whether one of these molecules might also be sending instructions to the brain.
Research shows that neural activation is much greater as measured with fos (magenta) when IL-1 beta was administered vs. when a control (vehicle) chemical was.
(Image Credit: Cho Lab/MIT Picower Institute)
They tested them one at a time. Injecting 21 different cytokines into mouse brains, they looked for anything that mimicked the same social drop-off seen during illness. Only interleukin-1 beta, or IL-1β — a molecule linked to inflammation — produced the full behavioral shift.
From there, they searched for where in the brain IL-1β could act. The molecule can only work when it binds its matching receptor, called IL-1R1. That search led to the dorsal raphe nucleus (DRN), a region involved in social behavior and home to many serotonin-producing neurons.
Read More: Mood Swings During Sickness Are Caused by Complex Brain-Immune Crosstalk
The Brain Circuit That Turns Off Social Behavior
With the DRN identified as the starting point, the team traced what these IL-1β-sensitive neurons do. Many release serotonin, a chemical tied to mood and social motivation — a hint that this pathway could be shaping more than fatigue.
When the researchers activated these neurons in healthy mice, the animals disengaged socially. Silencing the same neurons had the opposite outcome: sick mice stopped avoiding others, even though they still felt sluggish. That split suggests tiredness and social withdrawal come from two different biological systems, not one.
Next, the researchers looked at where these cells send their signals. Several downstream regions were linked to social behavior, but only one pathway reproduced the full effect. Using optogenetics — a technique that switches 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 sick instantly.
The same circuit engaged when the animals faced a real infection with salmonella, strengthening the case that this mechanism plays out in natural illness.
Bigger Questions About Sickness and the Brain
The study maps a pathway linking an immune signal to a neural circuit that drives social withdrawal, but the findings also leave several open questions.
It’s still unclear whether IL-1R1-expressing neurons contribute to other sickness behaviors, or whether serotonin produced by many of these cells plays a direct role in shaping the response.
Read More: Why Do I Get Sick So Often, While Others Stay in Freakishly Good Health?
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