Can our immune system regulate social behavior? Can it influence our desire to interact with others? The immune system is our main defense mechanism against disease.
Dysfunctions in the immune system are therefore associated with a myriad of complications, including several neurological and mental disorders.
Yet, for a long time the brain and the immune system were considered to be isolated from each other – it was believed that the brain was not supplied by the lymphatic system (which carries white blood cells and other immune cells through a network of vessels and tissues) because no evidence of lymphatic supply to the brain had ever been found.
Research on our immune system
But recently, a research team from the University of Virginia School of Medicine was able to find lymphatic vessels in the meninges that cover the brain. This was a huge discovery that shattered the long-standing belief that the brain was “immune privileged,” lacking a direct connection to the immune system.
After discovering the direct link between the brain and the lymphatic system, the same group has demonstrated that immune cells can influence learning behavior, exerting their effects apparently from the meninges, the membranes that cover the central nervous system.
Now, the same group has shown that the immune system has another surprising effect on the brain – it can directly affect, and even control social behavior, such as the desire to interact with others.
Link between the immune system and social behavior
Using mice with impaired immunity, the authors showed that partial elimination of immune cells from the meninges was sufficient to induce deficits in social behavior. These social deficits were reversed when the mice were repopulated with immune cells.
These immune impaired mice also exhibited hyper-connectivity in specific brain regions associated with social behavior. Again, repopulating mice with immune cells reversed the abnormal hyper-connectivity observed. Other functionally connected regions not directly implicated in social function were not affected by a deficiency in adaptive immunity.
Despite their proximity to the brain, immune cells in the meninges don’t enter the brain. Their effects, therefore, have to be exerted by releasing molecules that can cross into the brain. The authors were able to identify which molecule acts as a messenger between the immune system and the brain in regulating social behavior.
The molecule is called interferon gamma (IFN-gamma) and it can be produced by a substantial number of meningeal immune cells. Blocking the production of this molecule caused similar social deficits and abnormal hyper-connectivity in the same brain regions as in immune impaired mice.
Restoring the levels of the molecule restored the brain activity and behavioral patterns, through the action of IFN-gamma in GABAergic inhibitory neurons. Importantly, the authors also demonstrated that rodents living in a social context (group-housing) had natural increases in the production of IFN-gamma, whereas rodents in social isolation had a marked loss of IFN-gamma. Zebrafish and flies showed a similar pattern.