By affecting white blood cell populations, acute and chronic psychological stress can decrease a body’s ability to fight off infection, but how the brain communicates with the immune system to do this is unclear. Filip Swirski, a professor at the Icahn School of Medicine at Mount Sinai, New York, explores this form of inter-organ communication. “A big question is how do the various organs in our systems respond to external factors and lifestyle changes, whether that's sleep, diet, exercise, or stress, because our body systems really adapt to fluctuations in our environment,” said Swirski.
In a recent study published in Nature, Swirski and his group showed that inducing acute stress in mice caused profound changes in the immune system.1 Specifically, B and T cells left the lymph nodes and rapidly migrated to the bone marrow. “We were both very surprised to see how massive these immune shifts are within very short periods of stress,” said Wolfram Poller, a clinician-researcher and first author of the study. As a consequence, these stress-induced immune system shifts had a profound effect on disease susceptibility, decreasing a mouse’s ability to tolerate influenza or SARS-CoV-2 infections.
Next, Swirski’s team wanted to identify the specific brain networks that caused this physical change in the immune system. The researchers first explored the paraventricular hypothalamus (PVH), a region controlled by the sympathetic nervous system (SNS) that is important in stress and the fight or flight response. By activating or inactivating specific neurons in the PVH, the researchers found that they could induce or reduce leukocyte migration to the bone marrow. Because lymphatic tissues play a major role in immune tolerance, they modeled autoimmune disease in mice and found that when stressed, these mice displayed fewer detrimental outcomes, such as inflammation and paralysis, due to the immune cell migration away from the lymph nodes. These experiments revealed an important aspect of how psychological stress can dampen the responses leading to autoimmune disorders while also decreasing the body’s ability to withstand infectious disease.
“We were both very surprised to see how massive these immune shifts are within very short periods of stress.”
Wolfram Poller, Icahn School of Medicine at Mount Sinai, New York
Swirski’s team also found that in response to acute stress, neutrophils became more prevalent in multiple tissues. Neutrophils aid in the repair of tissue damage; therefore, their distribution to multiple areas in the body prepares it for possible injury. The scientists again looked at the SNS for answers and were surprised to find that it was not involved in the neutrophil response. Instead, they looked for neutrophil modulators in the blood and identified CXCL1, a protein in muscle that changed in response to stress. By inactivating or stimulating the specific motor circuit neurons in the brain known to control muscle movements, the researchers modulated the neutrophil response, making this study one of the first to find a direct mechanistic connection between a specific brain region and its effect on the immune system.
“What this paper does is it [goes] into the detailed brain pathways that are important in regulating different parts of the immune response,” said Esther Sternberg, the research director for the Andrew Weil Center for Integrative Medicine at the University of Arizona at Tucson, who was not involved in the study. “How elegant and miraculous is it that when you’re so stressed that you need to fight or flee—you could be injured—the immune system sends the neutrophils to exactly where they need to be.”
While stress prepares the body for injury, it also makes the body more susceptible to infectious disease by dampening other immune responses. Swirski and his group are now interested in the questions these findings raise about how people with socio-economic struggles deal with chronic or acute stressors and whether their bodies are prepared to deal with viral infections. “That relationship is something that I think is worth exploring, to inspect how some of these socio-economic factors really put our immune systems at a disadvantage,” said Swirski.
- W.C. Poller et al., “Brain motor and fear circuits regulate leukocytes during acute stress,” Nature, Epub ahead of print, 2022.