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Cited by 359

The DOI matches its Crossref record; 4 of the 4 references it cites were found in a registry or an index.

A Drug-Sensitive Genetic Network Masks Fungi from the Immune System

Open access
Wheeler, Robert T, Fink, Gerald R·2006·PLoS Pathogens
DOI 10.1371/journal.ppat.0020035
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Abstract

Fungal pathogens can be recognized by the immune system via their beta-glucan, a potent proinflammatory molecule that is present at high levels but is predominantly buried beneath a mannoprotein coat and invisible to the host. To investigate the nature and significance of "masking" this molecule, we characterized the mechanism of masking and consequences of unmasking for immune recognition. We found that the underlying beta-glucan in the cell wall of Candida albicans is unmasked by subinhibitory doses of the antifungal drug caspofungin, causing the exposed fungi to elicit a stronger immune response. Using a library of bakers' yeast (Saccharomyces cerevisiae) mutants, we uncovered a conserved genetic network that is required for concealing beta-glucan from the immune system and limiting the host response. Perturbation of parts of this network in the pathogen C. albicans caused unmasking of its beta-glucan, leading to increased beta-glucan receptor-dependent elicitation of key proinflammatory cytokines from primary mouse macrophages. By creating an anti-inflammatory barrier to mask beta-glucan, opportunistic fungi may promote commensal colonization and have an increased propensity for causing disease. Targeting the widely conserved gene network required for creating and maintaining this barrier may lead to novel broad-spectrum antimycotics.

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Cites

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Metadata

Authors
Wheeler, R. T., & Fink, G. R.
Venue
PLoS Pathogens
Publisher
Public Library of Science (PLoS)
Published
2006-04-28
Volume
2
Issue
4
Pages
e35
ISSN
  • 1553-7366 (ISSN-L)
  • 1553-7374
DOI
10.1371/journal.ppat.0020035
OpenAlex
W2074233079
Cited by
359
References
4
FWCI
17.40
Type
journal article
Language
en
Open access
gold
Licence
creativecommons.org/licenses/by/4.0/ (unspecified)

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