Enhanced killing of Candida albicans by human macrophages adherent to type 1 collagen matrices via induction of phagolysosomal fusion.
Enhanced killing of Candida albicans by human macrophages adherent to type 1 collagen matrices via induction of phagolysosomal fusion.
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通过诱导吞噬溶酶体融合，粘附于 1 型胶原基质的人巨噬细胞增强对白色念珠菌的杀灭。
DOI：
10.1128/iai.73.2.770-777.2005
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Morris,RandalE
中科院分区：
文献类型：
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作者：
Newman,SimonL;Bhugra,Bindu;Holly,Angela;Morris,RandalE
白色念珠菌是消化道和皮肤粘膜正常菌群的组成部分，是早产儿、糖尿病患者和外科患者侵袭性真菌病以及艾滋病患者口咽疾病的主要原因。由于对单核细胞/巨噬细胞抗念珠菌活性的调节知之甚少，我们试图确定杀菌活性是否可能受到体内单核细胞/巨噬细胞粘附的细胞外基质蛋白的调节。与粘附在塑料上的单核细胞/巨噬细胞相比，粘附在1型胶原基质上但不粘附在纤连蛋白、玻连蛋白或层粘连蛋白上的人单核细胞和单核细胞衍生的巨噬细胞显示出念珠菌活性显着增加。单核细胞杀菌活性的增强维持4小时以上，而巨噬细胞杀菌活性在1小时时达到最大。尽管单核细胞和巨噬细胞对胶原基质的粘附同时增强了超氧阴离子的产生，但仅粘附胶原的单核细胞的杀菌活性被超氧化物歧化酶和过氧化氢酶部分阻断。值得注意的是，我们发现 C 中只有 10% 的吞噬体。白色念珠菌感染的巨噬细胞粘附在与溶酶体融合的塑料上。相比之下，80% 含有酵母的胶原粘附巨噬细胞的吞噬体与溶酶体融合。这些数据表明非氧化机制对于人类巨噬细胞抗念珠菌活性至关重要，C.白色念珠菌的致病性部分是由其抑制巨噬细胞中吞噬溶酶体融合的能力介导的。
Candida albicans, a component of the normal flora of the alimentary tract and mucocutaneous membranes, is the leading cause of invasive fungal disease in premature infants, diabetics, and surgical patients and of oropharyngeal disease in AIDS patients. As little is known about the regulation of monocyte/macrophage anti-Candidaactivity, we sought to determine if fungicidal activity might be regulated by extracellular matrix proteins to which monocytes/macrophages are adherent in vivo. Compared to monocyte/macrophages that adhered to plastic, human monocytes and monocyte-derived macrophages that adhered to type 1 collagen matrices, but not to fibronectin, vitronectin, or laminin, demonstrated a significant increase in candidacidal activity. The enhancement of monocyte fungicidal activity was maintained over a 4-h period, whereas macrophage fungicidal activity was maximum at 1 h. Although adherence of monocytes and macrophages to collagen matrices concomitantly enhanced the production of superoxide anion, only the fungicidal activity of collagen-adherent monocytes was partially blocked by superoxide dismutase and catalase. Remarkably, we found that only 10% of the phagosomes inC. albicans-infected macrophages that adhered to plastic fused with lysosomes. In contrast, 80% of yeast-containing phagosomes of collagen-adherent macrophages fused with lysosomes. These data suggest that nonoxidative mechanisms are critical for human macrophage anti-Candidaactivity and thatC. albicanspathogenicity is mediated, in part, by its ability to inhibit phagolysosomal fusion in macrophages.