ABOVE: (Left) T lymphocytes (pink and green cells) and blood vessels (orange) under normal conditions. (Right) T lymphocytes (pink cells), with calcium in green, which indicates cells responding to nerve signals, and blood vessels in orange after administration of noradrenaline. Both images were taken inside the lymph nodes of live mice. 


The paper
S. Devi et al., “Adrenergic regulation of the vasculature impairs leukocyte interstitial migration and suppresses immune responses,” Immunity, doi:10.1016/j.immuni.2021.03.025, 2021. 

Five years ago, researchers led by Scott Mueller, an immunologist of the University of Melbourne in Australia, injected noradrenaline, a neurotransmitter associated with stress, directly into the veins of mice. Scientists have long known that acute stress—both psychological and physical—can impair immunity, and Mueller was looking for the mechanism responsible for the effect. 

The team used two-photon microscopy, a technique that allows researchers to look into live tissues, to examine how the mouse immune cells responded to the noradrenaline. Within minutes, the animals’ T cells stopped moving. Injection of other neurotransmitters, such as dopamine, did not have the same effect. 

To see how long the effect lasts and whether it diminished the animals’ ability to fight off infection, the researchers infected the mice with herpes simplex virus (HSV). After two days, they treated mice with a molecule called Iso that mimics the action of adrenaline by binding the same receptors, known as adrenergic receptors. Observing the animals’ lymph nodes with 2-photon microscopy, the researchers found that the Iso abruptly stopped the movement of T cells and dendritic cells for more than two hours. When they treated the mice with another adrenergic receptor agonist called salmeterol twice daily for three days, there were fewer virus-specific T cells at the infection site. The researchers conducted similar experiments with mice that had been injected with melanoma cells or malaria parasites. In both cases, mice treated with salmeterol showed inhibited immune responses with fewer pathogen or cancer-specific T cells.

The findings suggest that neurotransmitters released by neurons in the brain during stressful experiences cause immune cells to stop in their tracks rather than patrolling the body to identify and fight invaders, an observation Mueller calls “incredibly unexpected.”

Asya Rolls, who studies interactions between neuroscience and immunity but was not involved in the study, says the researchers “introduce a surprising mechanism of how the nervous system can regulate immune trafficking.”