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Antifungal immunity PI: Constantin Urban Department of Clinical Microbiology Contact: This e-mail address is being protected from spambots. You need JavaScript enabled to view it Our group is interested in the fundamental processes during infections with pathogenic fungi. We combine studies on how the innate immune system restricts the spread of fungal pathogens and how these microbes in turn react to the host environment. Candida albicans Severe infections caused by the pathogenic yeast Candida albicans are increasing in immunocompromised people worldwide. The mortality of these infections is high. Risk groups are patients with inherited or acquired immunodeficiencies, cancer, organ transplantations, etc. As the number of immunocomprised persons has increased over the last decade continuously, more life-threatening fungal infections have occurred as well. This situation demands new reliable therapeutics and diagnostics. Neutrophils Polymorphonuclear neutrophils are circulating cells of the innate immune system serving as first line of defense against microbial pathogens. They contain large numbers of granules in their cytoplasm and have a characteristically lobulated nucleus. Once recruited to the site of infection by proinflammatory signals neutrophils engulf microbes and kill them. Neutrophil apply a combination of non-oxidative (granule proteins) and oxidative mechanisms. A diverse set of reactive oxygen species (ROS) are formed upon activation of the NADPH oxidase complex. As recently described upon stimulation, neutrophils are additionally able to release Neutrophil Extracellular Traps (NETs). ROS production via the NADPH oxidase complex is required for NET formation. During the process the chromatin decondenses, the nuclear envelope disassembles, cytoplasmic and granular material mix and finally the plasma membrane ruptures to release NETs. This process describes a novel form of cell death. Known components of the NETs are DNA, histones and granular proteins, such as neutrophil elastase and myeloperoxidase. Research interests It is well established that neutrophils are crucial to control pathogenic fungi, as patients with acquired or inherited disorders of neutrophils often suffer from severe, life-threatening fungal infections. We want to understand how neutrophils contribute to defeat fungal pathogens. We have shown previously that NETs trap and kill fungi. However, the killing mechanism is not known. In a biochemical approach we have identified 24 different NET-associated proteins. We want to find out which NET proteins contribute to the antifungal activity during infections. This will furthermore enable us to identify the structures on the microbes which are targeted by these neutrophil proteins. We are moreover interested in characterizing the response of C. albicans to neutrophils and other immune cells to identify the microbe's immune evasion strategies. This knowledge might help to find novel strategies to control fungal disease. Figure legends: Fig. 01: SEM micrograph of a lung tissue section showing C. albicans hyphae ensnared in NETs 24 hours after challenge. Fig 02: SEM micrograph of an in vitro infection of human neutrophils with C. albicans showing a neutrophil that tries to engulf a hyphae (thin structure crossing the image). Swedish summary on the research of Constantin Urban and his group (on www.umu.se) Studying spores - fighting spungi, atricle about Constantin Urban's research in Researchmmedia.eu Iinternational Innovation is the leading global dissemination resource for the wider scientific, technology and research communities, dedicated to disseminating the latest science, research and technological innovations on a global level. More information and a complimentary subscription offer to the publication can be found at: www.researchmedia.eu)