Histidine-Rich Glycoprotein Protects from Systemic Candida Infection

PLoS Pathogens

Artur Schmidtchen¹  Willi Jahnen-Dechent²  Anna Chalupka³  Matthias Mörgelin³  Lukasz Kacprzyk⁴  Anna-Karin Olsson⁴  Katarina Lundqvist⁴  Victoria Rydengård⁴  Martin Malmsten⁵  Oonagh Shannon⁵ 

[1] Department of Biomedical Engineering, RWTH Aachen University Hospital, Aachen, Germany;Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala Biomedical Center, Uppsala, Sweden;Department of Microbiology, Faculty of Biochemistry, Biophysics & Biotechnology, Jagiellonian University, Kraków, Poland;Section of Dermatology and Venereology, Department of Clinical Sciences, Lund University, Biomedical Center, Lund, Sweden;Section of Infection Medicine, Department of Clinical Sciences, Lund University, Biomedical Center, Lund, Sweden

关键词: Antifungals;    C;    ida;    Blood plasma;    C;    ida albicans;    Fungi;    Histidine;    Liposomes;    Heparin;   

DOI  :  10.1371/journal.ppat.1000116

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Fungi, such as Candida spp., are commonly found on the skin and at mucosal surfaces. Yet, they rarely cause invasive infections in immunocompetent individuals, an observation reflecting the ability of our innate immune system to control potentially invasive microbes found at biological boundaries. Antimicrobial proteins and peptides are becoming increasingly recognized as important effectors of innate immunity. This is illustrated further by the present investigation, demonstrating a novel antifungal role of histidine-rich glycoprotein (HRG), an abundant and multimodular plasma protein. HRG bound to Candida cells, and induced breaks in the cell walls of the organisms. Correspondingly, HRG preferentially lysed ergosterol-containing liposomes but not cholesterol-containing ones, indicating a specificity for fungal versus other types of eukaryotic membranes. Both antifungal and membrane-rupturing activities of HRG were enhanced at low pH, and mapped to the histidine-rich region of the protein. Ex vivo, HRG-containing plasma as well as fibrin clots exerted antifungal effects. In vivo, Hrg−/− mice were susceptible to infection by C. albicans, in contrast to wild-type mice, which were highly resistant to infection. The results demonstrate a key and previously unknown antifungal role of HRG in innate immunity.

【 授权许可】

CC BY