The innate immune system is activated by stimulation of vaginal epithelial cells with Staphylococcus aureus and toxic shock syndrome toxin 1
The innate immune system is activated by stimulation of vaginal epithelial cells with Staphylococcus aureus and toxic shock syndrome toxin 1
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DOI：
10.1128/iai.73.4.2164-2174.2005
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发表时间：
2005-04-01
影响因子：
3.1
通讯作者：
Schlievert, PM
中科院分区：
文献类型：
--
作者：
Peterson, ML;Ault, K;Schlievert, PM
尽管了解中毒性休克综合征（TSS）毒素1（TSST-1）对适应性免疫系统的影响，但对先天性免疫系统（特别是上皮细胞）的刺激知之甚少。本研究调查了TSS金黄色葡萄球菌和TSST-1与人阴道上皮细胞（HVEC）和猪粘膜表面的相互作用。与HVECs共培养6 h，TSS S.金黄色葡萄球菌MN 8增殖，在HVEC表面形成聚集体，并产生外毒素。受体结合研究表明，S-35-TSST-1与每个HVEC 5 × 10（4）个受体结合，在15分钟时达到饱和。金黄色葡萄球菌MNSM（100个细菌/HVEC）在6小时内导致410个HVEC基因上调或下调至少两倍;这些数据也得到了S. aureus MN8. TSST-1（100 μ g/ml）在6 h内引起2，386个HVEC基因的上调或下调。响应S。在金黄色葡萄球菌中，与对照组相比，HVEC基因上调最多的是那些编码趋化因子或细胞因子的基因-MIP-3 α，478倍; GRO-α，26倍; GRO-β，14倍;和GRO-γ，30倍--提示先天免疫的激活。TSST-1还引起趋化因子/细胞因子基因的上调。通过酶联免疫吸附试验测定S. aureus和TSST-1。S.当与猪阴道组织一起孵育时，金黄色葡萄球菌MN 8增加了S-35-TSST-1穿过粘膜表面的通量。这伴随着淋巴细胞流入组织的上层。这些数据表明，通过上皮细胞的先天免疫系统激活，反映在趋化因子/细胞因子的产生和淋巴细胞的流入，可能会导致阴道粘膜通透性的变化，促进TSST-1渗透。
Despite knowledge of the effects of toxic shock syndrome (TSS) toxin 1 (TSST-1) on the adaptive immune system, little is known about stimulation of the innate immune system, particularly epithelial cells. This study investigated the interactions of TSS Staphylococcus aureus and TSST-1 with human vaginal epithelial cells (HVECs) and porcine mucosal surfaces. When cocultured with HVECs for 6 h, TSS S. aureus MN8 proliferated, formed aggregates on the HVEC surfaces, and produced exotoxins. Receptor binding studies showed that S-35-TSST-1 bound to 5 x 10(4) receptors per HVEC, with saturation at 15 min. Affymetrix Human GeneChip U133A microarray analysis determined S. aureus MNSM (100 bacteria/HVEC) caused at least twofold up- or down-regulation of 410 HVEC genes by 6 h; these data were also confirmed with S. aureus MN8. TSST-1 (100 mu g/ml) caused up- or down-regulation of 2,386 HVEC genes by 6 h. In response to S. aureus, the HVEC genes most up-regulated compared to those in controls were those coding for chemokines or cytokines-MIP-3 alpha, 478-fold; GRO-alpha, 26-fold; GRO-beta, 14-fold; and GRO-gamma, 30-fold-suggesting activation of innate immunity. TSST-1 also caused up-regulation of chemokine/cytokine genes. Chemokine/cytokine gene up-regulation was confirmed by enzyme-linked immunosorbent assays measuring the corresponding proteins induced by S. aureus and TSST-1. S. aureus MN8, when incubated with porcine vaginal tissue, increased the flux of S-35-TSST-1 across the mucosal surface. This was accompanied by influx of lymphocytes into the upper layers of the tissue. These data suggest innate immune system activation through epithelial cells, reflected in chemokine/cytokine production and influx of lymphocytes, may cause changes in vaginal mucosa permeability, facilitating TSST-1 penetration.