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Fungus sabotages phagocytes
When pathogens enter our body, they trigger a series of reactions: The immune system becomes active and begins to fight the intruder. Among other things, macrophages, i.e. scavenger cells, are involved. They take up the pathogen and kill it. An international research team from Jena, Great Britain, Portugal, Greece and the USA has now been able to show what role certain dynamic areas in the cell membrane of macrophages play in the fight against the pathogenic mold fungus Aspergillus fumigatus and how it attempts to escape the immune system. The scientists report on this in the scientific journal Cell Reports.
Macrophages are of great importance in the immune response to pathogens because they take up the pathogen, trap it and finally kill it. During this process, the phagocyte isolates the pathogen in a small compartment, the phagolysosome, thus rendering it harmless. "We were able to find out that lipid rafts, also known as lipid rafts, i.e. certain dynamic areas in the membrane, are of crucial importance in this process," says Axel Brakhage, who holds the Chair of Microbiology and Molecular Biology at the Friedrich Schiller University of Jena. "The lipid rafts are anchor points for proteins that ensure that the macrophage recognizes and kills the disease-causing organism. If these flotillin proteins found in the lipid rafts are affected by small genetic changes, patients have an increased risk of contracting a life-threatening Aspergillus fungal infection".
Camouflage through melanin
However, the mold Aspergillus fumigatus has a mechanism that sabotages this part of the immune response: The international group of scientists around Brakhage found out that the layer of the pigment melanin on spores of the fungus makes it difficult for the immune system to recognize them. This leads to less acidification of the phagolysosomes. This is fundamental, however, because when the pH drops, some enzymes become active and can kill the spores. This delays the reaction chain in the immune response. "The melanin works for the fungal spores like a camouflage suit. This gives the fungus time to spread and cause damage," explains Brakhage, "which is why we are trying to increase the antimicrobial activity of phagolysosomes with the help of targeted nanocontainers. The nanocontainers are hollow spheres that bring active ingredients in the body to their site of action in a targeted manner. The Collaborative Research Centre PolyTarget at the Friedrich Schiller University of Jena develops such carrier materials for the targeted application of active pharmaceutical ingredients.
F. Schmidt, A. Thywißen, M. Goldmann, C. Cunha, Z. Cseresnyés, H. Schmidt, M. Rafiq, S. Galiani, M. H. Gräler, G. Chamilos, J. F. Lacerda, A. Campos Jr., C. Eggeling, M. T. Figge, T. Heinekamp, S. G. Filler, A. Carvalho, A. A. Brakhage: Flotillin-Dependent Membrane Microdomains Are Required for Functional Phagolysosomes against Fungal Infections, Cell Reports (2020), https://doi.org/10.1016/j.celrep.2020.108017
Text: Alena Gold
Photo: Marie Goldmann