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Antifungal immunity

PI: Constantin Urban, Associate Professor
Department of Clinical Microbiology
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12679_candida_netsOur group "Antifungal Immunity" 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.

Background
Pathogenic fungi
Severe infections caused by opportunistic fungal pathogens, such as Candida albicans, Cryptococcus neoformans and Aspergillus fumigatus are increasing in immunocompromised people worldwide. The mortality of these infections is unacceptably high. Risk groups for invasive mycoses are immunocompromised patients with inherited or acquired immunodeficiencies, cancer and after organ transplantations or surgery. As the number of immunosuppressed persons has been continuously increasing, more life-threatening fungal infections occur worldwide. This situation demands new reliable therapeutics and diagnostics.

Research interests
Neutrophils
Neutrophils are crucial to control pathogenic fungi, as patients with acquired or inherited disorders of neutrophils often suffer from invasive, life-threatening fungal infections. We aim to understand how neutrophils contribute to defeat fungal pathogens. Excessive inflammation, however, frequently accompanies invasive mycoses worsening the patient's prognosis. We therefore aim to understand how inflammatory processes are down-regulated during fungal infections. Basic understanding of neutrophil killing mechanisms and regulation of inflammation will most probably help to identify better strategies to control fungal disease.

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)Mast cells
Fungi mostly enter the human body via mast cell (MC) rich tissue, such as the gastrointestinal and the respiratory tract, or colonize those as part of the commensal flora. MCs are leukocytes that reside immediately beneath epithelial surfaces lining the outer environment. Their direct hematopoietic progenitors remain unknown. MCs are recognized as crucial effector cells in IgE-mediated type I allergic diseases, such as for instance asthma. In contrast, their contributions to innate immunity are less well understood. Although MCs express receptor molecules that have been shown to bind fungal ligands in other contexts, the role of MCs in antifungal immunity is virtually unexplored. We therefore aim to understand how MCs recognize fungal pathogens and contribute to the recruitment and activation of other immune cells.

Screening for new antifungal agents
Inspired by the fact that human neutrophils are essential to control opportunistic fungal pathogens we are developing assays to identified small molecules mimicking different neutrophil activities. In collaboration with the Laboratory for Chemical Biology Umeå we are adapting these assays to high-throughput formats to screen for new antifungal compounds. The long-term goal is to identify molecules that can form the basis for the development of next-generation antimycotics.

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).

play Read more on the new webpage of the Urban group at the Department of Clinical Microbiology


playSwedish summary on the research of Constantin Urban and his group (on www.umu.se)
play pdfStudying spores - fighting spungi, atricle about Constantin Urban's research in Researchmedia.eu International 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)

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