How stress can stop immune cells in their tracks

Prof Scott Mueller & team (Dept Microbiology & Immunology at the Doherty Institute) use an advanced imaging technique to shed light on why we are more likely to get sick when we are stressed.

Image: Sympathetic nervous system

The group of researchers have discovered that signals produced by nerves in response to stress can stop immune cells from effectively fighting pathogens or tumours.

Led by Professor Scott Mueller, Laboratory Head in the Dept of Microbiology & Immunology at the Doherty Institute, the study made the striking observation that in response to a period of stress, immune cells ceased moving.

While the change is not permanent, stress can dramatically affect the way our immune system responds.

Published in Immunity, Professor Mueller and his team used an advanced imaging technique known as intravital microscopy to look at how stress impacts cells of the immune system of live mice in real time.

The team placed anaesthetised mice on a special platform that is placed under the microscope. The traditional lasers used for confocal microscopes are replaced with a high-powered two-photon laser, which allows imaging deeper into tissues with less damage from laser heating. The two-photon laser can also image molecules like collagen, enabling researchers to see these tissue structures.

Together, this allows researchers to make movies of the immune cells, pathogens and tissue structures.

We know anecdotally that when we are stressed, we are more likely to get sick, but exactly why this occurs has been difficult to define, until now. The imaging showed us that stress caused immune cells to stop moving, preventing them from protecting against disease

“Movement is central to how immune cells can get to the right parts of the body to mount an immune response against infections or tumours, so it was surprising to see that the stress signals had such a rapid and dramatic effect on how immune cells move around," said Professor Mueller.

“We also showed that it was different types of immune cells that were affected, and that it can occur in many different parts of the body.”

Professor Mueller says knowing how stress can impair immune responses may provide new avenues to overcome the negative effects of stress on immunity.

“For instance, cancer patients face increased stress that can contribute to a decreased ability of the body to fight the disease, and we might be able to use our findings to improve immune responses for those patients.”

He adds that there are many reasons why the body produces these signals from the nervous system, called neurotransmitters – they control heart rate and blood pressure, for instance. The team found that nerves don’t halt immune cells in all instances, only in response to significant stress.

“It’s also difficult to study what kind of stress signals could induce the immune cells to stop. Is it a sudden shock? Or chronic psychological stress?” says Professor Mueller.

The team are now using the findings to test immune responses to cancer.

“We are currently imaging models of breast cancer to understand how activation of the sympathetic nervous system impacts tumour development and anti-cancer immunity,” says Professor Mueller.

“The ultimate goal would be figuring out how we use these findings to boost anti-cancer responses in patients. At this stage, things are still in progress.”

This article was originally published by the Doherty Institute in 2022.

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