Overview: Research reveals how acute stress affects the brain’s control of immune response, impacting recovery from COVID-19 and flu.
Source: Mount Sinai Hospital
Acute stress can be detrimental to warding off infections, especially COVID-19, and increases the probability of death in mouse models.
This study is the first to show how specific regions in the brain regulate the body’s cellular immune response while under acute stress and infected with COVID-19 or the flu.
More specifically, it showed that acute stress triggers neurons from the region known as the paraventricular hypothalamus to immediately trigger a large-scale migration of white blood cells (immune cells or leukocytes) from lymph nodes into the blood and bone marrow.
This reduces the immune response to viruses such as COVID-19 and the flu, making the body less resistant to infection and at greater risk of complications and death.
This fundamental discovery linking the brain to the immune system provides a better understanding of how stress affects the body’s response to a virus, and why some are more susceptible to serious illness and worse outcomes.
Researchers first looked at groups of relaxed and stressed mouse models and analyzed their immune systems. Within minutes, mice experiencing acute stress showed major changes in their immune systems compared to the relaxed group of mice. In particular, stress caused a large migration of immune cells in the body from one location to another. Researchers wanted to explain this phenomenon.
Using advanced tools such as optogenetics and chemogenetics, the researchers found that neurons of the paraventricular hypothalamus prompt immune cells to migrate from lymph nodes into the blood and bone marrow.
Next, researchers went on to analyze how mice in the relaxed and stressed models compared when infected with the flu and COVID-19. They noticed that mice in the relaxed group did better compared to the stressed group — they fought infection better and got rid of the virus more easily.
Mice in the stressed group were sicker, had less immunity and had a higher mortality from the virus. The researchers also examined how other brain regions linked to motor function direct different types of immune cells that travel from the bone marrow to the blood.
Different brain regions make up the distribution of leukocytes and function throughout the body during acute stress in mice. The effect of stress on white blood cells and how it can negatively affect fighting a virus is important to better understand the results and find ways to improve immunity. If white blood cells are continuously released into the bloodstream, it can also have implications for cardiovascular health.
This study is an important example of how the brain controls inflammation and its association with reducing an immune response during acute stress.
This work may prompt doctors to look further into patients’ mental states, including sleep patterns and stress levels. It can prompt interventions to not only lead a healthier and less stressful lifestyle, but also help the body fight infection and improve outcomes.
“This work tells us that stress has a major impact on our immune system and its ability to fight infection. It raises a lot of questions about how socioeconomic factors, lifestyle and environments we live in determine how our bodies can defend against infection,” said Dr. Swirski.
“In the future, we will need to better understand the long-term effects of stress. It will be especially important to explore how we can build resilience to stress and whether resilience can reduce the negative effects of stress on our immune system.”
Financing: This study was funded by multiple grants from the National Heart, Lung and Blood Institute/NIH
About this stress and COVID-19 research news
Author: Ilana Nikravesh
Source: Mount Sinai Hospital
Contact: Ilana Nikravesh – Mount Sinai Hospital
Image: The image is in the public domain
Original research: Closed access.
“Brain motor and fear circuits regulate leukocytes during acute stress” by Swirski et al. Nature
Brain motor and fear circuits regulate leukocytes during acute stress
The nervous system and the immune system are closely linked. While psychological stress is known to modulate immune function, mechanistic pathways linking stress networks in the brain to peripheral leukocytes remain poorly understood.
Here we show that different brain regions determine the distribution of leukocytes and function throughout the body during acute stress in mice. Using optogenetics and chemogenetics, we demonstrate that motor circuits induce rapid mobilization of neutrophils from the bone marrow to peripheral tissues via skeletal muscle-derived neutrophil-attracting chemokines.
Conversely, the paraventricular hypothalamus controls the exit of monocytes and lymphocytes from secondary lymphoid organs and blood to the bone marrow through direct, cell-intrinsic glucocorticoid signaling. These stress-induced, opposing, population-wide shifts of leukocytes are associated with altered susceptibility to disease.
On the one hand, acute stress alters innate immunity by reprogramming neutrophils and directing their recruitment to sites of injury.
On the other hand, corticotropin releasing hormone (CRH) neuron-mediated leukocyte shifts protect against acquiring autoimmunity, but reduce immunity against SARS-CoV-2 and influenza infection.
Collectively, these data show that different brain regions differentially and rapidly adapt the leukocyte landscape during psychological stress, calibrating the immune system’s ability to respond to physical threats.