Nav: Home

Researchers find the immune system's unknown messenger

February 25, 2019

Researchers can now explain how a cell that is being attacked by bacteria or viruses specifically manages to 'sound the alarm' among its neighbouring cells so they can react with a quick response.

"We've succeeded in finding and describing a messenger which both quickly and effectively can inform the surrounding cells that something is very wrong and that the cells must therefore band together to fight the foreign micro-organisms" says Professor Søren Riis Paludan from the Department of Biomedicine at Aarhus University, Denmark.

He has today published the research results in the journal Nature Microbiology together with Assistant Professor Ramya Nandakumar and a large group of partners from Aarhus, Austria, France, Switzerland and Germany. Ramya Nandakumar can see a number of interesting perspectives in the new findings:

"The study sheds new light on how the organism quickly and effectively alarms the neighbourhood, and now that we know about the mechanism, it makes sense to continue working on when it might be advantageous to give it a boost to inhibit an infection, and vice versa, when it should be blocked in order to halt an autoimmune disease," says Ramya Nandakumar - we will return to this second point later.

On a general level, the findings fall under the scope of Søren Paludan's many years of work on understanding how the immune system recognises infections so that it is able to react with a quick and effective defence. This is a field of research that he has followed and moulded all the way from his postgraduate studies until today - driven by a desire to map how the innate immune system's cells respond to infection.

"As I see it, the immune system's recognition of micro-organisms is one of biology's most fundamental issues, and one that we, despite more than a century of research, still don't completely understand," says Søren Paludan.

"The fact that our bodies can be constantly exposed to foreign microorganisms in the form of viruses and bacteria is deeply fascinating, as is the fact that in the vast majority of instances it is able to distinguish between foreign and non-foreign. This is critical for our ability to fight microorganisms without our immune system attacking the body's own tissue," adds Søren Paludan.

In the study, researchers cultured cells exposed to the listeria bacteria which can cause the serious but rare type of food poisoning called Listeriosis.

In the petri dish, the researchers uncovered how the attacking listeria bacteria initially penetrated the cell, where they dumped a little of their DNA. The chunk of DNA was then distributed into the cytoplasm, which is the part of a cell that surrounds the cell nucleus. Here the protein cGAS discovered the foreign DNA, and along with the signal protein STING, sent alarm signals into the cell.

It is here that the newly-discovered messenger comes into the picture in the form of yet another protein, MVB12b, which is responsible for packing and exporting the DNA fragments in some fat bubbles called exosomes which resemble soap bubbles. They are then sent on to the neighbouring cell, where researchers have now documented that defensive responses can be started even before the cell is infected - with the protein simply being the unknown distributor. And this is important knowledge in the context of understanding, diagnosing and treating infectious diseases.

"This opens for the possibility of being able to 'turn up' the messenger so that it begins fighting the enemy even faster and can thus suppress the infection," says Søren Paludan.

In the study, the research group also experimented with 'turning down' the messenger. This was done in experiments with mice who were given listeria bacteria while the researchers at the same time studied the effects of blocking the exosomes' possibility of sending signals between cells.

"When we did this, the mice found it difficult to quickly spread an immune signal and thereby send an alarm signal to the tissue that needed protecting. This provides new perspectives in relation to the treatment of autoimmune diseases such as Lupus, which leads to pain in the joints, skin rashes and severe renal impairment," says Søren Paludan.

He explains that autoimmune diseases are also characterised by the cell nucleus beginning to spit small DNA fragments out into the cytoplasm, or the cells having difficulty breaking down DNA from dead cells. DNA therefore accumulates in the cytoplasm, without any external bacteria or virus coming into play.

"Here, the immune system's cells simply start fighting themselves instead of an enemy from outside, and of course, this raises the question of whether it is possible to block the messenger mechanism that we've now found and mapped with these auto-immune diseases. For example, there is considerable interest in the question of whether blocking STING has an effect against autoimmune diseases such as Lupus," says Søren Paludan.

Facts: The immune system - how it works

The body is under constant attack from foreign bacteria and viruses which occasionally penetrate into the body's cells, where specific molecules from the micro-organism - such as e.g. the foreign DNA, are recognised as an indication of an infection. When this happens, the immune system's cells rise to the occasion and fight the infection, whereupon we get better again.

When it comes to the autoimmune diseases, the body reacts exactly as above, but its reaction is not triggered by an infection, but by something that is "wrongly interpreted" as being foreign, such as e.g. the cell's own DNA. These long-term immune reactions make us ill, in some cases chronically.
-end-


Aarhus University

Related Immune System Articles:

The immune system may explain skepticism towards immigrants
There is a strong correlation between our fear of infection and our skepticism towards immigrants.
New insights on how pathogens escape the immune system
The bacterium Salmonella enterica causes gastroenteritis in humans and is one of the leading causes of food-borne infectious diseases.
Understanding how HIV evades the immune system
Monash University (Australia) and Cardiff University (UK) researchers have come a step further in understanding how the human immunodeficiency virus (HIV) evades the immune system.
Carbs during workouts help immune system recovery
Eating carbohydrates during intense exercise helps to minimise exercise-induced immune disturbances and can aid the body's recovery, QUT research has found.
A new model for activation of the immune system
By studying a large protein (the C1 protein) with X-rays and electron microscopy, researchers from Aarhus University in Denmark have established a new model for how an important part of the innate immune system is activated.
Guards of the human immune system unraveled
Dendritic cells represent an important component of the immune system: they recognize and engulf invaders, which subsequently triggers a pathogen-specific immune response.
How our immune system targets TB
Researchers have seen, for the very first time, how the human immune system recognizes tuberculosis (TB).
How a fungus inhibits the immune system of plants
A newly discovered protein from a fungus is able to suppress the innate immune system of plants.
A new view of the immune system
Pathogen epitopes are fragments of bacterial or viral proteins. Nearly a third of all existing human epitopes consist of two different fragments.
TB tricks the body's immune system to allow it to spread
Tuberculosis tricks the immune system into attacking the body's lung tissue so the bacteria are allowed to spread to other people, new research from the University of Southampton suggests.

Related Immune System Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Jumpstarting Creativity
Our greatest breakthroughs and triumphs have one thing in common: creativity. But how do you ignite it? And how do you rekindle it? This hour, TED speakers explore ideas on jumpstarting creativity. Guests include economist Tim Harford, producer Helen Marriage, artificial intelligence researcher Steve Engels, and behavioral scientist Marily Oppezzo.
Now Playing: Science for the People

#524 The Human Network
What does a network of humans look like and how does it work? How does information spread? How do decisions and opinions spread? What gets distorted as it moves through the network and why? This week we dig into the ins and outs of human networks with Matthew Jackson, Professor of Economics at Stanford University and author of the book "The Human Network: How Your Social Position Determines Your Power, Beliefs, and Behaviours".