Plaine Armêl, Yáñez Alberto, Murciano Celia, Gaillardin Claude, Gil M Luisa, Richard Mathias L, Gozalbo Daniel
Laboratoire de Microbiologie et Génétique Moléculaire, AgroParisTech, UMR-INRA1238 UMR-CNRS2585, 78850 Thiverval-Grignon, France.
Microbes Infect. 2008 Apr;10(4):382-9. doi: 10.1016/j.micinf.2007.12.018. Epub 2008 Jan 9.
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.
白色念珠菌gpi7/gpi7基因敲除突变株（Δgpi7）在糖基磷脂酰肌醇（GPI）锚定生物合成方面存在缺陷，在对C57BL/6小鼠进行全身感染后，其毒力有所降低。与对照（野生型GPI7/GPI7和回复株gpi7/GPI7）细胞相比，巨噬细胞对Δgpi7细胞产生的肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）和白细胞介素-1β（IL-1β）的体外产量显著增加；这可能有助于增强中性粒细胞对Δgpi7细胞的反应而向腹腔的募集。静脉注射Δgpi7细胞后，Toll样受体（TLR）2和TLR4基因敲除小鼠的存活率与C57BL/6小鼠相比无显著差异。在体外，巨噬细胞产生TNF-α以及中性粒细胞募集在TLR2-/-小鼠中对对照酵母菌株的反应中受到显著抑制。有趣的是，在所有三种类型的小鼠中，对Δgpi7的反应中TNF-α的产生和中性粒细胞的募集均显著增加，且它们之间无差异，海带多糖未能抑制TNF-α的这种增加的产生。这些结果表明，对Δgpi7增强的促炎反应不涉及通过TLR2、TLR4或dectin-1的识别。因此，完整的GPI锚赋予了表面特性，这些特性参与调节巨噬细胞对白色念珠菌的细胞因子产生反应。
