Over 200,000 deaths are caused by the dangerous mold fungus Aspergillus fumigatus

Promising approach in the treatment of mold Aspergillus fumigatus

A dangerous disease-causing fungus called Aspergillus fumigatus costs around 200,000 people worldwide each year. In addition, many millions of people suffer from lung diseases and allergies such as asthma. A refurbished research team has now succeeded in taking a promising approach to reducing the consequences of fungal infection in the future.

An international team of scientists, with a study recently published in the journal "Nature", sheds new light on the immune reaction of our body to a dangerous disease-causing fungus. Every year, it causes around 200,000 deaths and causes lung disease and allergies in millions of patients, such as asthma. With the participation of the Friedrich Schiller University Jena, the researchers found a clue that could now help in the fight against the deadly fungus.

Infection with the fungus Aspergillus fumigatus is one of the most dreaded complications for patients undergoing surgery such as transplantation. In a weakened immune system, the naturally occurring mold fungus can enter the bloodstream and cause an infection of the internal organs up to a sepsis. Over 50% of patients die from it. Aspergillus fumigatus is so dangerous because it is very difficult to diagnose and treat. For this reason, scientists have long been trying to understand how the human immune system recognizes the fungus. This understanding is important in order to develop therapies that activate the body's defenses.

How does the immune system detect the dangerous intruder??

Working together with many predominantly European institutions, the researchers, led by Professor Gordon Brown of the University of Aberdeen, identified a novel mechanism: the body's immune system responds to an unexpected component of the fungus, melanin. The dye is recognized by a specific receptor called MelLec and a reaction of the immune system follows. So far, science has assumed that the immune system primarily recognizes sugar in the cell wall of fungi.
Some variants of the receptor can even increase the susceptibility to infections in the course of medical treatments such as transplantation, as the research group also found.

Professor Gordon Brown, director of the Medical Research Council Center for Medical Mycology at the University of Aberdeen, summarizes the findings of the study: "A better understanding of how our immune system responds to the intruder is crucial to making it better in infected people recognize and develop new therapies. We have now shown that our immune system reacts to parts of the fungus that we did not know before they were detected. While this discovery is a big step forward, it also highlights how complex the fight against these fungi is. "

What Jena scientists contributed

From Germany Prof. Dr. Ing. Axel Brakhage involved in the research. He is a professor at the Friedrich Schiller University Jena and director of the Leibniz Institute for Natural Product Research and Infection Biology. As one of the most renowned experts in fungal infections, he had discovered the biosynthetic pathway of the pigment melanin and its importance for the pathogenic effect of the fungus.

Comparative studies using the mutant fungi he produced showed that the receptor MelLec binds exactly to this dye formed by the fungus. "It fascinates me that in the course of evolution has developed its own receptor for the mushroom melanin. This indicates that the dye plays an important role in humans in an infection, "he comments on the breakthrough. Furthermore, the microbiologist states: "Such complex processes as the colonization of humans by fungi and the immune response directed against them can no longer be investigated by a single group or even a scientist alone. We are very pleased with the Europe-wide network of experienced researchers, who are studying the different aspects of fungal infections at the molecular level and bringing together the knowledge gained. The successful fight against infections is only possible across national borders ", affirms the Jena University Professor.

Dr. dr. Betty Hebecker, another author of the Nature article, this international collaboration. She completed her doctoral thesis at the Leibniz Institute for Natural Product Research and Infection Biology in Jena. She then moved to Aberdeen with a grant from the Deutsche Forschungsgemeinschaft as a postdoc in Gordon Brown's group.

Original publication:
Stappers MHT, Clark AE, Aimanianda V, Bidula S, Reid DM, Asamaphan P, Hardison SE, Dambuza IM, Valsecchi I, Kerscher B, Plato A, Wallace CCA, Yuecel R, Hebecker B, since Glória Teixeira Sousa M, Cunha C , Liu Y, Feizi T, Brakhage AA, Kwon-Kung KJ, Gow NAR, Zanda M, Piras M, Zanato C, Jaeger M, Netea MG, van de Veerdonk FL, Lacerda JF, Campos A, Carvalho A, Willment YES, Latgé JP, Brown GD (2018): Recognition of DHN-melanin by a C-type lectin receptor is required for immunity to Aspergillus. Nature.

Involved institutions:
Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Radboud University Medical Center, University of Lisbon, Instituto Português de Oncologia do Porto. Contact in Jena: Prof. Dr. med. Axel Brakhage