How the Immune System Controls Social Behavior

Researchers have found a new mechanism that could explain the link between social dysfunction and immune dysfunction.

Carlos Barria / Reuters

More and more, we are discovering that the mind and the body are not separate. The brain is not just an ivory tower that sends orders from on high to a body that just does what it’s told. The body talks to the brain, too. Indeed, a group of scientists recently discovered a two-way connection between the brain and the immune system, one that could have far-reaching implications.

For the longest time, scientists thought that the brain was totally separate from the body’s immune system—recent work has shown that’s not so. In the membranes that cover the brain and spinal cord, there are lymphatic vessels that can drain fluid and immune cells from the cerebrospinal fluid into the deep cervical lymph nodes, which are located in the neck. Researchers identified these vessels first in mice, then found a “potentially similar structure” in humans.

That was in 2015. Now, a new study has shown that the immune system’s connections with the central nervous system may actually affect how animals behave socially. The key is a molecule called interferon-gamma. T-cells, a type of white blood cell, in those vessels emit interferon-gamma (let’s just call it I-G, not to be confused with Instagram) into the brain. Once there, it inhibits neurons in the prefrontal cortex. This is normal—without I-G, that region can become overactive. And researchers have found that in mice, when the prefrontal cortex becomes overactive, they get asocial.

Why would more brain activity make an animal less social? “I like the example of traffic,” says Vladimir Litvak, a professor at the University of Massachusetts Medical School, and an author on the study. “Too much traffic actually causes the stop of traffic. The system is unable to process all these signals.”

The researchers looked at several kinds of animals—rats, mice, zebrafish, and fruit flies—and found that when they gathered together, certain genes would activate and this I-G response would flare up. (Except the flies, who don’t actually have I-G, but they do have similar genes that activate.)

Immune system dysfunction is linked to several diseases that involve social dysfunction—dementia, schizophrenia, and autism spectrum disorder among them. It could be that I-G is the link that explains this connection.

“We were really fascinated by why this antipathogen molecule would have a prosocial function—that doesn't really make sense,” says Anthony Filiano, a postdoctoral researcher at the University of Virgnia, and lead author on the study. Socializing helps animals in tons of ways, sure, but gathering in groups makes diseases more likely to spread. Why, evolutionarily speaking, is that something the immune system would want to promote?

On this, the researchers can only speculate. “Naturally if individuals tend to spread diseases, that could easily result in extinction of the whole colony,” Litvak says. “So you have to have a very strong immune response.” Maybe the immune system activates when animals are socializing to protect them against the increased risk of getting a disease.

Fililano suggests the possibility of a more complicated co-evolution between animals and the pathogens that infect them. It could be that viruses evolved to try to trigger this response, so animals would be more social, and spread the viruses further. And then, the animals in turn evolved so the immune system would protect them even when they were being social.

“We think we've recycled these pro-social genes as an anti-pathogen response,” Filiano says.

Whatever the reason, this research opens a new pathway by which to understand and investigate social behavior. I-G levels in humans’ blood vary throughout the day, Litvak says, “so maybe at some part of the day we’ll be more social, or less social.” And in terms of treating and understanding social dysfunction associated with disorders, the immune system is “easier to target than synapses in the brain,” Filiano says. Plus, I-G is just one of hundreds of molecules secreted by the immune system—the others could give us even more insight into the brain and behavior.