Crippling effects of Aspergillus fumigatus on the human immune system

The crippling effects of Aspergillus fumigatus on the human immune system
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According to University of Jena, Germany, a toxic substance from the fungus Aspergillus fumigatus, can threaten the lives of people with a compromised immune system.

The fungus Aspergillus fumigatus occurs virtually everywhere on Earth, as a form of dark grey padding on damp walls or in microscopically small spores that blow through the air and cling to wallpaper, mattresses and floors. Those with a healthy immune system usually experience 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 those who are AIDS patients or individuals who are immunosuppressed following an organ transplantation.

Aspergillus fumigatus breaks down the defence system of the immune system

Available to read in Cell Chemical Biology, an international research team led by Professor Oliver Werz of Friedrich Schiller University (or University of Jena), has now uncovered how the fungus Aspergillus fumigatus knocks out the immune defences, enabling a potentially fatal fungal infection to develop.

Among other factors, it is gliotoxin, a potent mycotoxin, that is responsible for the pathogenicity of Aspergillus fumigatus.

Werz explains: “It was known 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.

The communication of immune cells

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 meets 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 can switch off enzymes

This does not occur 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.” concludes Werz.

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