Immune sensing of Candida albicans requires cooperative recognition of mannans and glucans by lectin and Toll-like receptors
Immune sensing of Candida albicans requires cooperative recognition of mannans and glucans by lectin and Toll-like receptors
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DOI：
10.1172/jci27114
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发表时间：
2006-06-01
影响因子：
15.9
通讯作者：
Kullberg, Bart Jan
中科院分区：
文献类型：
--
作者：
Netea, Mihai G.;Gow, Neil A. R.;Kullberg, Bart Jan
真菌病原体白色念珠菌具有多层细胞壁，由 N- 或 O- 连接甘露糖基残基糖基化的蛋白质外层和 β-葡聚糖和几丁质内骨架层组成。我们证明，当受到甘露糖基化缺陷的白色念珠菌突变体刺激时，人单核细胞或鼠巨噬细胞产生的细胞因子显着减少。甘露糖残基的识别是通过与N-连接的甘露糖残基结合的甘露糖受体和与O-连接的甘露糖残基结合的TLR4介导的。残余细胞因子的产生是通过 dectin-1/TLR2 受体复合物识别 β-葡聚糖介导的。细胞壁甘露糖残基缺陷的白色念珠菌突变体在实验性播散性念珠菌病中毒性较低，并引起体内细胞因子产生减少。我们得出的结论是，单核细胞/巨噬细胞对白色念珠菌的识别是由 3 个不同重要性的识别系统介导的，每个识别系统都感知白色念珠菌细胞壁的特定层。
The fungal pathogen Candida albicans has a multilayered cell wall composed of an outer layer of proteins glycosylated with N- or O-linked mannosyl residues and an inner skeletal layer of beta-glucans and chitin. We demonstrate that cytokine production by human mononuclear cells or murine macrophages was markedly reduced when stimulated by C. albicans mutants defective in mannosylation. Recognition of mannosyl residues was mediated by mannose receptor binding to N-linked mannosyl residues and by TLR4 binding to O-linked mannosyl residues. Residual cytokine production was mediated by recognition of beta-glucan by the dectin-1/TLR2 receptor complex. C albicans mutants with a cell wall defective in mannosyl residues were less virulent in experimental disseminated candidiasis and elicited reduced cytokine production in vivo. We concluded that recognition of C albicans by monocytes/macrophages is mediated by 3 recognition systems of differing importance, each of which senses specific layers of the C. albicans cell wall.