Modulation of MICA on the surface of Chlamydia trachomatis-infected endocervical epithelial cells promotes NK cell-mediated killing.
Modulation of MICA on the surface of Chlamydia trachomatis-infected endocervical epithelial cells promotes NK cell-mediated killing.
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DOI：
10.1111/j.1574-695x.2012.00930.x
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发表时间：
2012-06
影响因子：
--
通讯作者：
Schust DJ
中科院分区：
文献类型：
--
作者：
Ibana JA;Aiyar A;Quayle AJ;Schust DJ
沙眼衣原体血清型 D-K 是专性细胞内细菌，对生殖道的柱状上皮细胞具有趋向性。据报道，沙眼衣原体感染可诱导上皮宿主细胞上免疫细胞配体表达的改变。在这项研究中，我们使用了体外感染模型，该模型导致暴露于沙眼衣原体的原代样永生化宫颈上皮细胞（A2EN）的部分感染。使用该模型，我们证明自然杀伤 (NK) 细胞激活配体、MHC I 类相关蛋白 A (MICA) 的表达在沙眼衣原体感染的细胞中上调，但在未感染的旁观者细胞上则没有上调。 MICA 上调伴随着 I 类 MHC 下调，并影响沙眼衣原体感染细胞对 NK 细胞活性的敏感性。与未感染的对照细胞相比，NK 细胞系 (NK92MI) 对沙眼衣原体感染的细胞具有更高的细胞溶解活性，反映了 MICA 上调的特异性。值得注意的是，数据还表明，NK 细胞对沙眼衣原体发挥了部分但不完全的灭菌作用，如与沙眼衣原体感染的细胞共培养时可恢复包涵体形成单位 (IFU) 的减少所示。综上所述，我们的数据表明 NK 细胞可能在宿主抵抗沙眼衣原体感染的能力中发挥重要作用。
Chlamydia trachomatis serovars D-K are obligate intracellular bacteria that have tropism for the columnar epithelial cells of the genital tract. Chlamydia trachomatis infection has been reported to induce modifications in immune cell ligand expression on epithelial host cells. In this study, we used an in vitro infection model that resulted in a partial infection of C. trachomatis-exposed primary-like immortalized endocervical epithelial cells (A2EN). Using this model, we demonstrated that expression of the natural killer (NK) cell activating ligand, MHC class I-related protein A (MICA), was upregulated on C. trachomatis-infected, but not on noninfected bystander cells. MICA upregulation was concomitant with MHC class I downregulation and impacted the susceptibility of C. trachomatis-infected cells to NK cell activity. The specificity of MICA upregulation was reflected by a higher cytolytic activity of an NK cell line (NK92MI) against C. trachomatis-infected cells compared with uninfected control cells. Significantly, data also indicated that NK cells exerted a partial, but incomplete sterilizing effect on C. trachomatis as shown by the reduction in recoverable inclusion forming units (IFU) when cocultured with C. trachomatis-infected cells. Taken together, our data suggest that NK cells may play a significant role in the ability of the host to counter C. trachomatis infection.