Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

How a fungus can cripple the immune system

07.02.2019

Research team from the University of Jena clarifies the mechanism of gliotoxin, a mycotoxin from the fungus Aspergillus fumigatus

It is everywhere – and it is extremely dangerous for people with a weakened immune system. The fungus Aspergillus fumigatus occurs virtually everywhere on Earth, as a dark grey, wrinkled cushion on damp walls or in microscopically small spores that blow through the air and cling to wallpaper, mattresses and floors.


Petri dish with the fungus Aspergillus fumigatus.

Credit: Jan-Peter Kasper/FSU


Dr Thorsten Heinekamp of the Jena research team inspects a petri dish with the fungus Aspergillus fumigatus.

Credit: Jan-Peter Kasper/FSU

Healthy people usually have no problem if spores find their way into their body, as their immune defence system will put the spores out of action.

However, the fungus can threaten the lives of people with a compromised immune system, such as AIDS patients or people who are immunosuppressed following an organ transplantation.

An international research team led by Prof. Oliver Werz of Friedrich Schiller University, Jena, has now discovered how the fungus knocks out the immune defences, enabling a potentially fatal fungal infection to develop.

The researchers present their findings in the current issue of the specialist journal Cell Chemical Biology (DOI: 10.1016/j.chembiol.2019.01.001).

Among other factors, it is gliotoxin – a potent mycotoxin – that is responsible for the pathogenicity of Aspergillus fumigatus. “It was known,” says study manager Werz of the Institute of Pharmacy at the University of Jena, “that this substance has an immunosuppressive effect, which means that it weakens the activity of cells of the immune defence system.”

However, it had not been clear previously how exactly this happens. Werz and his team colleagues have now studied this in detail and have clarified the underlying molecular mechanisms.

Immune cells communicate with one another

To achieve this, the researchers brought immune cells into contact with synthetically produced gliotoxin. These cells, called neutrophilic granulocytes, represent the first line of the immune defence system.

“Their task is to detect pathogens and eliminate them,” explains Werz. As soon as such a cell comes into contact with a pathogen, for example a fungus, it releases specific messenger substances (leukotrienes) into the blood, which attract other immune cells. Once a sufficiently large number of immune cells has gathered, they can render the intruder harmless.

Mycotoxin switches off enzyme

This does not happen if the pathogen Aspergillus fumigatus is involved. As the Jena scientists were able to show, gliotoxin ensures that production of the messenger substance leukotrieneB4 in the neutrophilic granulocytes is inhibited, so that they are unable to send a signal to other immune cells.

This is caused by a specific enzyme (LTA4 hydrolase) being switched off by the mycotoxin. “This interrupts communication between the immune cells and destroys the defence mechanism. As a result, it is easy for spores – in this case the fungus – that enter the organism to infiltrate tissues or organs,” says Werz.

Cooperation in Cluster of Excellence ‘Balance of the Microverse’

For their study, Prof. Werz and his colleagues collaborated with researchers from the Leibniz Institute for Natural Product Research and Infection Biology (Hans Knöll Institute). As part of the Collaborative Research Centre ChemBioSys and the Jena Cluster of Excellence ‘Balance of the Microverse’, they cooperated with the working groups led by Prof. Axel Brakhage and Prof. Christian Hertweck, which contributed their expertise in mycology and natural product synthesis. Additional partners are research groups from the Universities of Frankfurt and Naples, as well as the Karolinska Institute in Stockholm.

Wissenschaftliche Ansprechpartner:

Prof. Oliver Werz
Institute of Pharmacy of Friedrich Schiller University, Jena
Philosophenweg 14, 07743 Jena, Germany
Tel.: +49 (0)3641 / 949801
E-mail: oliver.werz@uni-jena.de

Originalpublikation:

König S et al. Gliotoxin from Aspergillus fumigatus Abrogates Leukotriene B4 Formation through Inhibition of Leukotriene A4 Hydrolase, Cell Chemical Biology 26, 1-11 (2019), DOI: 10.1016/j.chembiol.2019.01.001, https://www.cell.com/cell-chemical-biology/fulltext/S2451-9456(19)30001-7

Dr. Ute Schönfelder | idw - Informationsdienst Wissenschaft
Further information:
http://www.uni-jena.de/

More articles from Life Sciences:

nachricht Finally available in a bottle
07.02.2019 | Albert-Ludwigs-Universität Freiburg im Breisgau

nachricht An Elegant Mechanism
07.02.2019 | Albert-Ludwigs-Universität Freiburg im Breisgau

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Finally available in a bottle

Researchers succeed in gaining access to an important chemical compound

Since the discovery of the first homoleptic metal carbonyl complex Ni(CO)4 more than 130 years ago, scientists try to obtain further such compounds formed from...

Im Focus: Escort service: The role of immune cells in the formation of metastases

Tumor cells use a certain type of immune cells, the so-called neutrophils, to enhance their ability to form metastases. Scientists have deciphered the mechanisms of this collaboration and found strategies for blocking them. This is reported by researchers from the University of Basel and the University Hospital of Basel in the scientific journal "Nature".

A better understanding of the features that define the interplay between cancer cells and immune cells is key to identifying new cancer therapies. Yet, focus...

Im Focus: Invisible tags: Physicists at TU Dresden write, read and erase using light

A team of physicists headed by Prof. Sebastian Reineke of TU Dresden developed a new method of storing information in fully transparent plastic foils. Their innovative idea was now published in the renowned online journal “Science Advances”.

Prof. Reineke and his LEXOS team work with simple plastic foils with a thickness of less than 50 µm, which is thinner than a human hair. In these transparent...

Im Focus: IT in cars: Computers on standby

In the future, cars will exchange data via radio and warn each other about obstacles and accidents. There are currently various radio standards in existence to allow this. However, it is almost impossible to compare them, because the requisite hardware is not yet on the market. To address this lack, researchers at the Fraunhofer Institute for Telecommunications, Heinrich Hertz Institute, HHI have developed a software system that will enable users to analyze the future wireless technology. For manufacturers, this is an ideal solution for testing interesting radio applications at an early stage.

Slowly but surely, the automobile is developing into the autonomous vehicle, as new functions are added with each new generation. Proximity radars are by now...

Im Focus: Making ultrafast lasers faster

Lasers with ultrashort pulses in the picosecond and femtosecond range are often referred to as ultrafast lasers. They are known for their ultra-precise ablation and cutting results. Unfortunately, processing with such lasers takes time. To address this issue, a new research project, funded by the European Commission, aims to make material processing with ultrafast lasers up to a hundred times faster.

Ultrashort pulsed (USP) or ultrafast lasers can do something very unique: They ablate almost any material without causing a thermal load of the adjacent...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

The world of quantum chemistry meets in Heidelberg

30.01.2019 | Event News

Our digital society in 2040

16.01.2019 | Event News

11th International Symposium: “Advanced Battery Power – Kraftwerk Batterie” Aachen, 3-4 April 2019

14.01.2019 | Event News

 
Latest News

Scientists discover new type of magnet

07.02.2019 | Physics and Astronomy

Physicists take big step in nanolaser design

07.02.2019 | Physics and Astronomy

First look: Chang'e lunar landing site

07.02.2019 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>