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/

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: A cavity leads to a strong interaction between light and matter

Researchers have succeeded in creating an efficient quantum-mechanical light-matter interface using a microscopic cavity. Within this cavity, a single photon is emitted and absorbed up to 10 times by an artificial atom. This opens up new prospects for quantum technology, report physicists at the University of Basel and Ruhr-University Bochum in the journal Nature.

Quantum physics describes photons as light particles. Achieving an interaction between a single photon and a single atom is a huge challenge due to the tiny...

Im Focus: Solving the mystery of quantum light in thin layers

A very special kind of light is emitted by tungsten diselenide layers. The reason for this has been unclear. Now an explanation has been found at TU Wien (Vienna)

It is an exotic phenomenon that nobody was able to explain for years: when energy is supplied to a thin layer of the material tungsten diselenide, it begins to...

Im Focus: An ultrafast glimpse of the photochemistry of the atmosphere

Researchers at Ludwig-Maximilians-Universitaet (LMU) in Munich have explored the initial consequences of the interaction of light with molecules on the surface of nanoscopic aerosols.

The nanocosmos is constantly in motion. All natural processes are ultimately determined by the interplay between radiation and matter. Light strikes particles...

Im Focus: Shaping nanoparticles for improved quantum information technology

Particles that are mere nanometers in size are at the forefront of scientific research today. They come in many different shapes: rods, spheres, cubes, vesicles, S-shaped worms and even donut-like rings. What makes them worthy of scientific study is that, being so tiny, they exhibit quantum mechanical properties not possible with larger objects.

Researchers at the Center for Nanoscale Materials (CNM), a U.S. Department of Energy (DOE) Office of Science User Facility located at DOE's Argonne National...

Im Focus: Novel Material for Shipbuilding

A new research project at the TH Mittelhessen focusses on the development of a novel light weight design concept for leisure boats and yachts. Professor Stephan Marzi from the THM Institute of Mechanics and Materials collaborates with Krake Catamarane, which is a shipyard located in Apolda, Thuringia.

The project is set up in an international cooperation with Professor Anders Biel from Karlstad University in Sweden and the Swedish company Lamera from...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

International Symposium on Functional Materials for Electrolysis, Fuel Cells and Metal-Air Batteries

02.10.2019 | Event News

NEXUS 2020: Relationships Between Architecture and Mathematics

02.10.2019 | Event News

Optical Technologies: International Symposium „Future Optics“ in Hannover

19.09.2019 | Event News

 
Latest News

Kirigami inspires new method for wearable sensors

22.10.2019 | Materials Sciences

3D printing, bioinks create implantable blood vessels

22.10.2019 | Medical Engineering

Ionic channels in carbon electrodes for efficient electrochemical energy storage

22.10.2019 | Power and Electrical Engineering

VideoLinks
Science & Research
Overview of more VideoLinks >>>