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首页> 外文学位 >Antigen trafficking within Chlamydia trachomatis-infected polarized human endometrial epithelial cells.
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Antigen trafficking within Chlamydia trachomatis-infected polarized human endometrial epithelial cells.

机译：沙眼衣原体感染的极化人子宫内膜上皮细胞内的抗原运输。

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摘要

Chlamydia trachomatis serovars D-K are the leading cause of bacterially-acquired sexually transmitted infections in the United States. As an obligate intracellular pathogen, C. trachomatis infects columnar epithelial cells of the genital mucosae and can cause deleterious sequelae such as pelvic inflammatory disease, infertility, and ectopic pregnancy. Several chlamydial antigens reach the host cell cytosol prior to the natural release of chlamydiae at the end of the developmental cycle. While some of these extra-inclusion antigens traffic to the host cell surface, others remain intracellular where they are proposed to influence vital host cell functions and antigen trafficking and presentation. The research herein examines the escape and trafficking of the immunodominant chlamydial antigens MOMP, LPS, and cHsp60 within C. trachomatis serovar E-infected polarized human endometrial epithelial cells. Studies using high-resolution transmission electron microscopy (TEM) and immuno-TEM report the novel escape mechanism of chlamydial antigens via vesicles everted/pinched off from the inclusion membrane, an occurrence observed both in the presence and absence of the antibiotic azithromycin. These extra-inclusion vesicles were differentiated from Golgi vesicles and were shown to deliver chlamydial heat shock protein 60 (cHsp60)-homologs 2 and 3, but not homolog 1, to the infected cell surface. Examination of the iron-responsiveness of the three cHsp60 homologs by immuno-TEM revealed a significant increase in cHsp60-2 following iron deprivation. Further investigation of the trafficking of chlamydial MOMP and LPS antigens enveloped within the protective everted inclusion membrane vesicles within host cells involved density gradient centrifugation for the separation of epithelial secretory pathway components followed by SDS-PAGE and Western blot to determine whether the chlamydial antigen-containing vesicles could fuse with and deliver the antigens to host cell organelles. Coupled with immuno-TEM, these data confirmed the presence of major chlamydial antigens within the endoplasmic reticulum of infected host cells. Additionally, chlamydial lipopolysaccharide (LPS) was co-localized with CD1d, a lipid antigen-presenting molecule. Collectively, these studies (i) establish a novel escape mechanism for chlamydial antigens, (ii) identify cHsp60-2 as a marker of iron stress response in C. trachomatis, and (iii) define for the first time the host cell ER as a destination for selected chlamydial antigens during infection.
机译：在美国，沙眼衣原体血清型D-K是细菌获得性传播感染的主要原因。作为专一的细胞内病原体，沙眼衣原体可感染生殖器粘膜的柱状上皮细胞，并可引起有害的后遗症，例如盆腔炎，不孕症和异位妊娠。在发育周期结束时，衣原体自然释放之前，有几种衣原体抗原到达宿主细胞的胞质溶胶。尽管其中一些包容性抗原运往宿主细胞表面，但其他抗原仍保留在细胞内，因此它们会影响重要的宿主细胞功能以及抗原运输和呈递。本文的研究检查了沙眼衣原体血清型E感染的极化人子宫内膜上皮细胞内免疫优势衣原体抗原MOMP，LPS和cHsp60的逃逸和运输。使用高分辨率透射电子显微镜（TEM）和免疫TEM的研究报告了衣原体抗原通过从包涵膜外翻/夹出的囊泡中逃逸的新机制，在存在和不存在阿奇霉素的情况下均观察到这种情况。这些包涵体囊泡从高尔基囊泡分化，并显示将衣原体热休克蛋白60（cHsp60）同源2和3，但不是同源1传递到感染的细胞表面。通过免疫TEM检测三个cHsp60同源物的铁反应性表明，铁被剥夺后，cHsp60-2明显增加。进一步研究包裹在宿主细胞内保护性外翻包涵体膜囊泡中的衣原体MOMP和LPS抗原的运输，涉及密度梯度离心以分离上皮分泌途径成分，然后进行SDS-PAGE和Western印迹以确定是否含有衣原体抗原囊泡可与抗原融合并传递抗原至宿主细胞器。结合免疫TEM，这些数据证实了感染的宿主细胞内质网内存在主要的衣原体抗原。另外，衣原体脂多糖（LPS）与脂质抗原呈递分子CD1d共定位。总而言之，这些研究（i）建立了衣原体抗原的新型逃逸机制，（ii）将cHsp60-2鉴定为沙眼衣原体铁应激反应的标志物，并且（iii）首次将宿主细胞ER定义为沙眼衣原体。感染期间选定衣原体抗原的目的地。

著录项

  • 作者

    Giles, David K.;

  • 作者单位

    East Tennessee State University.;

  • 授予单位 East Tennessee State University.;
  • 学科 Biology Microbiology.
  • 学位 Ph.D.
  • 年度 2008
  • 页码 167 p.
  • 总页数 167
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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