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Enhanced proinflammatory response to the Candida albicans gpi7 null mutant by murine cells.

Abstract
The Candida albicans gpi7/gpi7 null mutant strain (Deltagpi7), which is affected in glycosylphosphatidylinositol (GPI) anchor biosynthesis, showed a reduced virulence following systemic infection of C57BL/6 mice. In vitro production of TNF-alpha, IL-6 and IL-1beta by macrophages in response to Deltagpi7 cells was significantly increased as compared to control (wild type GPI7/GPI7 and revertant gpi7/GPI7) cells; this probably contributes to the enhanced recruitment of neutrophils to the peritoneal cavity in response to Deltagpi7 cells. Survival of knockout mice for Toll-like receptor (TLR) 2 and TLR4 following intravenous injection of Deltagpi7 cells showed no significant differences as compared to C57BL/6 mice. In vitro production of TNF-alpha by macrophages and neutrophil recruitment were significantly inhibited in TLR2-/- mice in response to control yeast strains. Interestingly both TNF-alpha production and neutrophil recruitment in response to Deltagpi7 were significantly increased in all three types of mice, with no differences among them, and laminarin failed to inhibit this increased production of TNF-alpha. These results indicate that the enhanced proinflammatory response to Deltagpi7 does not involve recognition through TLR2, TLR4 nor dectin-1. Therefore, complete GPI anchors confer surface properties that are involved in modulation of cytokine production by macrophages in response to C. albicans.
AuthorsArmêl Plaine, Alberto Yáñez, Celia Murciano, Claude Gaillardin, M Luisa Gil, Mathias L Richard, Daniel Gozalbo
JournalMicrobes and infection (Microbes Infect) Vol. 10 Issue 4 Pg. 382-9 (Apr 2008) ISSN: 1286-4579 [Print] France
PMID18403244 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Fungal Proteins
  • Glycosylphosphatidylinositols
  • Interleukin-1beta
  • Interleukin-6
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • Tumor Necrosis Factor-alpha
  • Virulence Factors
Topics
  • Animals
  • Candida albicans (genetics, immunology)
  • Cells, Cultured
  • Fungal Proteins (genetics, immunology)
  • Gene Deletion
  • Glycosylphosphatidylinositols (genetics, immunology)
  • Inflammation (immunology, microbiology)
  • Interleukin-1beta (biosynthesis)
  • Interleukin-6 (biosynthesis)
  • Macrophages, Peritoneal (immunology, microbiology)
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neutrophils (immunology)
  • Peritoneal Cavity (pathology)
  • Survival Analysis
  • Toll-Like Receptor 2 (deficiency)
  • Toll-Like Receptor 4 (deficiency)
  • Tumor Necrosis Factor-alpha (biosynthesis)
  • Virulence
  • Virulence Factors (genetics, immunology)

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