Histidine-rich glycoprotein protects from systemic Candida infection.
(2008) In PLoS Pathogens 4(8).- Abstract
- 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... (More)
- 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1242928
- author
- Rydengård, Victoria LU ; Shannon, Oonagh LU ; Lundqvist, Katarina LU ; Kacprzyk, Lukasz ; Chalupka, Anna LU ; Olsson, Anna-Karin ; Mörgelin, Matthias LU ; Jahnen-Dechent, Willi ; Malmsten, Martin LU and Schmidtchen, Artur LU
- organization
- publishing date
- 2008
- type
- Contribution to journal
- publication status
- published
- subject
- in
- PLoS Pathogens
- volume
- 4
- issue
- 8
- article number
- e1000116
- publisher
- Public Library of Science (PLoS)
- external identifiers
-
- wos:000259783100004
- pmid:18797515
- scopus:50849136178
- ISSN
- 1553-7366
- DOI
- 10.1371/journal.ppat.1000116
- language
- English
- LU publication?
- yes
- id
- f89d3aa4-b9f2-408c-9619-28e643030dbf (old id 1242928)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/18797515?dopt=Abstract
- date added to LUP
- 2016-04-04 07:48:46
- date last changed
- 2022-04-23 08:39:54
@article{f89d3aa4-b9f2-408c-9619-28e643030dbf, abstract = {{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.}}, author = {{Rydengård, Victoria and Shannon, Oonagh and Lundqvist, Katarina and Kacprzyk, Lukasz and Chalupka, Anna and Olsson, Anna-Karin and Mörgelin, Matthias and Jahnen-Dechent, Willi and Malmsten, Martin and Schmidtchen, Artur}}, issn = {{1553-7366}}, language = {{eng}}, number = {{8}}, publisher = {{Public Library of Science (PLoS)}}, series = {{PLoS Pathogens}}, title = {{Histidine-rich glycoprotein protects from systemic Candida infection.}}, url = {{http://dx.doi.org/10.1371/journal.ppat.1000116}}, doi = {{10.1371/journal.ppat.1000116}}, volume = {{4}}, year = {{2008}}, }