2023-09-04 22:04:25
05.09.2023
Blood poisoning from a fungal infection is a life-threatening hazard. Researchers at the University of Bern have now discovered a mechanism that helps a yeast fungus to spread more easily within the body.
The immune system plays a key role in this. These findings might open up new therapeutic options for blood poisoning caused by yeast fungi, but also for other internal fungal infections.
Normally, the yeast fungus Candida albicans is a harmless cohabitant of our mucous membranes. Around half of the population is inhabited by it without noticing it. As long as the body’s defense system is intact, it effortlessly keeps the fungus in check. It becomes dangerous when the immune system is weakened. This can be the case, for example, with diseases such as AIDS or when taking medication that suppresses the immune system.
In people with a healthy immune system, surgical interventions that damage the mucosal barrier, among other things, can promote the spread of Candida albicans. Once the yeast fungus is in the bloodstream, it can cause blood poisoning (sepsis) and thus lead to permanent damage to the internal organs: A third to half of patients do not survive such fungal sepsis.
The immune system’s natural response to invading pathogens is an inflammatory response. A sophisticated control system ensures that only intruders are attacked without attacking healthy tissue at the same time. A key role is played by a specific protein, the so-called interleukin 1 receptor antagonist. This protein is the natural antagonist of the pro-inflammatory signaling substance interleukin 1. It prevents this from overshooting the target and triggering uncontrolled inflammatory reactions.
Anti-inflammatories weaken the immune system
A new study led by PD Dr. medical Stefan Freigang from the Institute of Tissue Medicine and Pathology (IGMP) at the University of Bern now suggests that the interleukin 1 receptor antagonist (IL-1Ra), despite its anti-inflammatory function, helps promote the spread of Candida albicans. IL-1Ra, which are formed by the so-called scavenger cells (macrophages), seem to be of particular importance.
In mice, the researchers were able to show that the amount of these anti-inflammatory proteins in the scavenger cells increased when Candida albicans entered the bloodstream, and that they then disrupted the immune system. Namely, they inhibited the production and swarming of neutrophils, a subset of white blood cells. The neutrophils form an important early barrier once morest infection by regularly patrolling the blood vessels to eliminate invading pathogens.
Mice that were genetically bred so that their phagocytes no longer produced the anti-inflammatory proteins had an intact arsenal of neutrophils. Accordingly, they were able to successfully combat an infection with Candida albicans within a short period of time. In contrast, in the control group of normal mice that produced the anti-inflammatory protein, the fungi were able to spread because of the inhibited neutrophils.
Interestingly, the loss of the anti-inflammatory proteins did not lead to an overshoot of the inflammatory response, as might have been expected, but to a reduction. “We explain this by the fact that there were enough neutrophils to eliminate the yeast before it might trigger a disease-causing inflammatory reaction,” says Stefan Freigang.
So if less anti-inflammatory proteins are produced, the neutrophils can do their work undisturbed as the “first line of defense”. However, if the proteins are formed by the scavenger cells, this weakens the immune system. Such complex and dynamic interactions of the immune system can only be depicted in a living organism, which in this case requires animal experiments with genetically modified and normal mice as a control group.
Possible therapeutic approach
The research results of the Bernese researchers might enable new therapeutic approaches in the future. “Fungal sepsis is still difficult to treat and associated with a high mortality rate. In order to be able to develop more effective treatment strategies, a better understanding of the underlying disease mechanisms is needed,” explains Stefan Freigang. In a next step, the researchers want to use patient samples to confirm the observations from the mouse model and investigate whether the specific protein also promotes infections with Candida albicans in humans. “If this is confirmed, active ingredients that target the protein might be used as a new strategy to combat yeast and possibly other fungal infections as well,” says Freigang.
The research results were published in the journal Immunity.
Those: University of Bern
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