Kim Hee Sup, Choi Eun Hwa, Khan Javed, Roilides Emmanuel, Francesconi Andrea, Kasai Miki, Sein Tin, Schaufele Robert L, Sakurai Kenichi, Son Chang Gue, Greer Braden T, Chanock Stephen, Lyman Caron A, Walsh Thomas J
Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute/NIH, Room 1-5740, Bethesda, MD 20892, USA.
Infect Immun. 2005 Jun;73(6):3714-24. doi: 10.1128/IAI.73.6.3714-3724.2005.
Little is known about the regulation and coordinated expression of genes involved in the innate host response to Candida albicans. We therefore examined the kinetic profile of gene expression of innate host defense molecules in normal human monocytes infected with C. albicans using microarray technology. Freshly isolated peripheral blood monocytes from five healthy donors were incubated with C. albicans for 0 to 18 h in parallel with time-matched uninfected control cells. RNA from monocytes was extracted and amplified for microarray analysis, using a 42,421-gene cDNA chip. Expression of genes encoding proinflammatory cytokines, including tumor necrosis factor alpha, interleukin 1 (IL-1), IL-6, and leukemia inhibitory factor, was markedly enhanced during the first 6 h and coincided with an increase in phagocytosis. Expression of these genes returned to near baseline by 18 h. Genes encoding chemokines, including IL-8; macrophage inflammatory proteins 1, 3, and 4; and monocyte chemoattractant protein 1, also were strongly up-regulated, with peak expression at 4 to 6 h, as were genes encoding chemokine receptors CCR1, CCR5, CCR7, and CXCR5. Expression of genes whose products may protect monocyte viability, such as BCL2-related protein, metallothioneins, CD71, and SOCS3, was up-regulated at 4 to 6 h and remained elevated throughout the 18-h time course. On the other hand, expression of genes encoding T-cell-regulatory molecules (e.g., IL-12, gamma interferon, and transforming growth factor beta) was not significantly affected during the 18-h incubation. Moreover, genes encoding IL-15, the IL-13 receptor (IL-13Ra1), and CD14 were suppressed during the 18-h exposure to C. albicans. Thus, C. albicans is a potent inducer of a dynamic cascade of expression of genes whose products are related to the recruitment, activation, and protection of neutrophils and monocytes.
关于宿主对白色念珠菌天然免疫反应中相关基因的调控及协同表达，我们知之甚少。因此，我们运用微阵列技术检测了感染白色念珠菌的正常人单核细胞中天然宿主防御分子基因表达的动力学特征。从五名健康供体新鲜分离的外周血单核细胞与白色念珠菌共孵育0至18小时，同时设置时间匹配的未感染对照细胞。从单核细胞中提取RNA并进行扩增，用于微阵列分析，使用的是包含42,421个基因的cDNA芯片。编码促炎细胞因子（包括肿瘤坏死因子α、白细胞介素1（IL-1）、IL-6和白血病抑制因子）的基因表达在最初6小时内显著增强，且与吞噬作用的增加同时出现。这些基因的表达在18小时时恢复到接近基线水平。编码趋化因子（包括IL-8、巨噬细胞炎性蛋白1、3和4以及单核细胞趋化蛋白1）的基因也强烈上调，在4至6小时达到表达峰值，编码趋化因子受体CCR1、CCR5、CCR7和CXCR5的基因也是如此。其产物可能保护单核细胞活力的基因（如BCL2相关蛋白、金属硫蛋白、CD71和SOCS3）的表达在4至6小时上调，并在整个18小时的时间进程中保持升高。另一方面，编码T细胞调节分子（如IL-12、γ干扰素和转化生长因子β）的基因在18小时的孵育过程中未受到显著影响。此外，在暴露于白色念珠菌18小时期间，编码IL-15、IL-13受体（IL-13Ra1）和CD14的基因受到抑制。因此，白色念珠菌是一系列基因动态表达级联反应的有力诱导剂，这些基因的产物与中性粒细胞和单核细胞的募集、激活及保护有关。
