Promising approach in the treatment of mold Aspergillus fumigatus
A dangerous disease-causing fungus called Aspergillus fumigatus costs the lives of around 200,000 people worldwide every year. In addition, many millions of people develop lung diseases and allergies such as asthma. A refurbished team of researchers has now succeeded in taking a promising approach to reduce the consequences of the fungal infection in the future.
An international team of scientists recently sheds new light on our body's immune response to a dangerous disease-causing fungus with a study recently published in the journal Nature. It claims around 200,000 lives annually and causes lung diseases and allergies, for example asthma, in millions of patients. 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 Aspergillus fumigatus fungus is one of the most feared complications for patients after surgery, such as a transplant. With a weakened immune system, the naturally occurring mold can get into the bloodstream and cause infection of the internal organs and even sepsis. Over 50% of the 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 to develop therapies that activate the body's defenses.
How does the immune system register the dangerous intruder?
In collaboration with numerous predominantly European institutions, the researchers, led by Professor Gordon Brown from the University of Aberdeen, identified a new mechanism: Our body's immune system reacts to an unexpected component of the fungus, melanin. The dye is recognized by a specially responsible 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 transplants, 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 results of the study: “A better understanding of how our immune system responds to the intruder is critical to making it better for infected people to recognize and develop new therapies. We have now demonstrated that our immune system reacts to parts of the fungus that we did not previously know were recognized. While this discovery is a big step forward, it also underscores the complexity of the fight against these mushrooms. ”
What Jena scientists contributed
From Germany was Prof. Dr. Axel Brakhage involved in the research. He is a professor at the Friedrich Schiller University in 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 discovered the biosynthetic pathway of the pigment melanin and its importance for the disease-causing effects of the fungus.
Comparative investigations with the help of the fungal mutants he produced showed that the MelLec receptor binds precisely this dye formed by the fungus. “I am fascinated that in the course of evolution a separate receptor for mushroom melanin has developed. This indicates that the dye plays an important role in humans when infected, ”he comments on the breakthrough. The microbiologist continues: “Such complex processes as the colonization of humans by fungi and the immune response against them can no longer be investigated by a single group or even a scientist alone. We are very happy about the Europe-wide network of experienced researchers, which examines the various aspects of fungal infections at the molecular level and brings together the knowledge gained. The successful fight against infections is only possible across national borders, ”affirmed the Jena university professor.
Dr. demonstrates particularly impressively 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. Afterwards she moved to Aberdeen with a grant from the German Research Foundation as a postdoc in Gordon Brown's group.
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, da Glória Teixeira Sousa M, Cunha C , Liu Y, Feizi T, Brakhage AA, Kwon-Chung KJ, Gow NAR, Zanda M, Piras M, Zanato C, Jaeger M, Netea MG, van de Veerdonk FL, Lacerda JF, Campos A, Carvalho A, Willment JA, Latgé JP, Brown GD (2018): Recognition of DHN-melanin by a C-type lectin receptor is required for immunity to Aspergillus. Nature.
Institut Pasteur, University of Minho, Imperial College London, Friedrich Schiller University Jena, Leibniz Institute for Natural Product Research and Infection Biology, National 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. Axel Brakhage