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Published on: February 18, 2015
Enhanced proinflammatory response to the Candida albicans gpi7 null mutant by murine cells
Armêl Plaine1, Alberto Yáñez, Celia Murciano
1Laboratoire de Microbiologie et Génétique Moléculaire, AgroParisTech, UMR-INRA1238 UMR-CNRS2585, 78850 Thiverval-Grignon, France.
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.
Insights
Candida albicans lacking GPI anchor biosynthesis (Deltagpi7) shows reduced virulence but triggers a heightened inflammatory response. This enhanced response in macrophages is independent of Toll-like receptors 2 and 4 (TLR2/TLR4) and dectin-1.
Area of Science:
- Mycology
- Immunology
- Molecular Biology
Background:
- Glycosylphosphatidylinositol (GPI) anchors are essential for Candida albicans cell wall integrity and virulence.
- The precise mechanisms by which C. albicans modulates host immune responses are not fully understood.
Purpose of the Study:
- To investigate the role of GPI anchor biosynthesis in C. albicans virulence and host immune cell activation.
- To determine the involvement of Toll-like receptors (TLRs) and dectin-1 in the immune response to C. albicans GPI mutants.
Main Methods:
- Generation of a Candida albicans gpi7/gpi7 null mutant (Deltagpi7) affecting GPI anchor biosynthesis.
- Systemic infection models in C57BL/6 mice and knockout mice for TLR2 and TLR4.
- In vitro assessment of macrophage cytokine production (TNF-alpha, IL-6, IL-1beta) and neutrophil recruitment.
Main Results:
- Deltagpi7 mutant exhibited reduced virulence in mice compared to wild-type strains.
- Macrophages produced significantly higher levels of TNF-alpha, IL-6, and IL-1beta in response to Deltagpi7.
- The enhanced pro-inflammatory response to Deltagpi7 was independent of TLR2, TLR4, and dectin-1 recognition.
Conclusions:
- Complete GPI anchors on C. albicans modulate macrophage cytokine production.
- The absence of GPI anchors leads to an increased inflammatory response not mediated by TLR2, TLR4, or dectin-1.
- GPI anchors play a critical role in immune evasion and virulence of C. albicans.
