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Histidine-rich glycoprotein protects from systemic Candida infection.

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 and Schmidtchen, Artur LU (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)
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author
organization
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type
Contribution to journal
publication status
published
subject
in
PLoS Pathogens
volume
4
issue
8
publisher
Public Library of Science
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
2008-10-07 15:03:08
date last changed
2017-10-22 04:52:42
@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.},
  articleno    = {e1000116},
  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},
  series       = {PLoS Pathogens},
  title        = {Histidine-rich glycoprotein protects from systemic Candida infection.},
  url          = {http://dx.doi.org/10.1371/journal.ppat.1000116},
  volume       = {4},
  year         = {2008},
}