Nav: Home

How a fungus can cripple the immune system

February 08, 2019

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. 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.
-end-
Original publication: Koenig 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

Contact:
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

Friedrich-Schiller-Universitaet Jena

Related Immune Cells Articles:

Identification of new populations of immune cells in the lungs
In an article published in Nature Communications, the Immunophysiology Laboratory of the GIGA Institute, headed by Prof.
A genomic barcode tracker for immune cells
A new research method to pinpoint the immune cells that recognise cancer could significantly change how we treat the disease.
Scientists reminded immune cells on what side they should be
International group of scientists in the joint study of the laboratory of the Wistar Institute, University of Pittsburgh and I.M.
Dead cells disrupt how immune cells respond to wounds and patrol for infection
Immune cells prioritise the clearance of dead cells overriding their normal migration to sites of injury.
Study gives new perspective on production of blood cells and immune cells
A new study provides a thorough accounting of blood cell production from hematopoietic stem cells.
Gut immune cells play by their own rules
Only a few vaccines -- for example, against polio and rotavirus -- can be given orally.
Revealed: How the 'Iron Man' of immune cells helps T cells fight infection
The immune system's killer T cells are crucial in fighting viral infections.
A bad influence: the interplay between tumor cells and immune cells
Research at Huntsman Cancer Institute (HCI) at the University of Utah (U of U) yielded new insights into the environment surrounding different types of lung tumors, and described how these complex cell ecosystems may in turn ultimately affect response to treatment.
Immune cells help older muscles heal like new
The immune system's macrophage cells are critical to growing muscle tissues in a lab, say the biomedical engineers at Duke University who earlier reported the world's first self-healing lab-grown muscles.
How damaging immune cells develop during tuberculosis
Insights into how harmful white blood cells form during tuberculosis infection point to novel targets for pharmacological interventions, according to a study published in the open-access journal PLOS Pathogens by Valentina Guerrini and Maria Laura Gennaro of Rutgers New Jersey Medical School, and colleagues.
More Immune Cells News and Immune Cells Current Events

Top Science Podcasts

We have hand picked the top science podcasts of 2019.
Now Playing: TED Radio Hour

Risk
Why do we revere risk-takers, even when their actions terrify us? Why are some better at taking risks than others? This hour, TED speakers explore the alluring, dangerous, and calculated sides of risk. Guests include professional rock climber Alex Honnold, economist Mariana Mazzucato, psychology researcher Kashfia Rahman, structural engineer and bridge designer Ian Firth, and risk intelligence expert Dylan Evans.
Now Playing: Science for the People

#540 Specialize? Or Generalize?
Ever been called a "jack of all trades, master of none"? The world loves to elevate specialists, people who drill deep into a single topic. Those people are great. But there's a place for generalists too, argues David Epstein. Jacks of all trades are often more successful than specialists. And he's got science to back it up. We talk with Epstein about his latest book, "Range: Why Generalists Triumph in a Specialized World".
Now Playing: Radiolab

Dolly Parton's America: Neon Moss
Today on Radiolab, we're bringing you the fourth episode of Jad's special series, Dolly Parton's America. In this episode, Jad goes back up the mountain to visit Dolly's actual Tennessee mountain home, where she tells stories about her first trips out of the holler. Back on the mountaintop, standing under the rain by the Little Pigeon River, the trip triggers memories of Jad's first visit to his father's childhood home, and opens the gateway to dizzying stories of music and migration. Support Radiolab today at Radiolab.org/donate.