Human brains are built for socialization. They evolved to support and thrive on the complex interpersonal behaviors required for species survival. Exactly how that came about is still unclear, but social neurologists generally believe the benefits of pair bonds and two-parent child-rearing drove the process.
In a curious twist, it now seems germs may have been involved, too.
According to recent research, our immune-system responses may directly control some aspects of our personalities.
In a study published in the journal Nature in July, neuroscientists from the University of Massachusetts' medical school and the University of Virginia medical school's Kipnis Lab discovered they could control socialization behavior in mice by manipulating immune activity in the rodents' brains.
Like Flipping a Switch
To determine the social effects of disabling a particular immune response, the researchers timed how long mice spent checking each other out under both normal and immune-deficient conditions.
"Normal mice are very social and will always have a preference to investigate another mouse," Jonathan Kipnis, co-author on the Nature paper and chair of UVA's department of neuroscience, writes in an email.
That inquisitive behavior changed when they genetically blocked the signaling pathways of interferon gamma (IFN-γ), a protein secreted by immune-system cells to battle pathogens. Mice without IFN-γ spent less time checking out other mice. When the researchers reopened the pathways, the mice returned to their normal levels of social interest.
The findings raise the possibility that humans are, as Kipnis told UVA Today, "just multicellular battlefields for two ancient forces: pathogens and the immune system."
The Neuro-immune Connection
To fully grasp the significance of the discovery, it helps to know that until last year, science thought the immune system didn't reach the brain. According to anatomy textbooks, the mammalian brain has no lymphatics, the vessels that carry infection-fighting molecules almost everywhere else in the body.
In 2015, UVA scientists found the brain's lymphatics. (So did a research team from the University of Helsinki, around the same time, in a totally separate study, using a different method.) The news was revolutionary. For many, it was like finding a missing link.
Immune activity can have profound impacts on the brain, as in multiple sclerosis, a brain disorder caused by a malfunctioning immune system. And scientists have long seen a connection between behavior and immunity. Geriatric psychologist William Matteson notes that multiple sclerosis is often misdiagnosed as a mental illness due to the personality changes that can accompany it. Brain disorders like autism, Alzheimer's disease and schizophrenia, which have strong behavioral components, present with immune dysfunction. Anxiety disorders and depression have immune features, too.
In the search for effective treatments, if immune dysfunction is a cause and not a symptom, it changes everything.
An Evolving Relationship
Anthony J. Filiano, a neurology fellow in the Kipnis Lab and lead author of the latest study, says research from multiple sources is starting to bear out a causal relationship, especially in behaviors like learning and memory.
"A lot of the action of the immune system is initiated in a tissue's draining lymph node," Filiano explains in an email, "and we published a study in 2014 showing that surgically removing the deep cervical lymph nodes in mice caused memory impairment."
If immune activity enables normal socialization, as well, it could have dramatic implications for disease research. It suggests immune responses and social behavior evolved in tandem, which makes sense: Social species can't survive if socialization spreads disease. IFN-γ may serve to protect people from pathogens while they interact with others, in which case the immune system has some control over how we socialize — and a malfunctioning immune system could disrupt the brain activity that regulates healthy social behavior.
The New Neuroscience
While the findings are exciting, Kipnis is cautious.
"Determining if the immune system 'controls' human social behavior can only be speculated," he writes. "However, we know that directly manipulating the immune system in mice results in social deficits."
If the findings do translate to humans, it points to countless new, neuro-immune avenues of research for myriad brain conditions that feature both immune and social dysfunction, including autism, Alzheimer's and a slew of psychiatric disorders.
It also highlights what Kipnis sees as a disconnect in his field.
"Unlike what is thought by some neuroscientists," he writes, "[the] brain's health and proper function is dependent on many cells, including the immune cells." Focusing on neurons alone, Kipnis says, is inhibiting our understanding of the brain.
"We should train the future generation of neuroscientists to be open-minded," he writes, "and to realize that there are more than neurons to neuroscience, no matter how important the neuron is as the functional unit."
The lab is currently exploring a role for the newly discovered brain lymphatics in multiple sclerosis and Alzheimer's disease.