Porcella Stephen F, Carlson John H, Sturdevant Daniel E, Sturdevant Gail L, Kanakabandi Kishore, Virtaneva Kimmo, Wilder Hannah, Whitmire William M, Song Lihua, Caldwell Harlan D
Genomics Unit Research Technologies Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA
Laboratory of Intracellular Parasites, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.
Infect Immun. 2015 Feb;83(2):534-43. doi: 10.1128/IAI.02764-14. Epub 2014 Nov 17.
Chlamydia trachomatis is an obligate intracellular epitheliotropic bacterial pathogen of humans. Infection of the eye can result in trachoma, the leading cause of preventable blindness in the world. The pathophysiology of blinding trachoma is driven by multiple episodes of reinfection of conjunctival epithelial cells, producing an intense chronic inflammatory response resulting in submucosal tissue remodeling and scarring. Recent reports have shown that infection with trachoma organisms lacking the cryptic chlamydial plasmid is highly attenuated in macaque eyes, a relevant experimental model of human trachoma infection. To better understand the molecular basis of plasmid-mediated infection attenuation and the potential modulation of host immunity, we conducted transcriptional profiling of human epithelial cells infected with C. trachomatis plasmid-bearing (A2497) and plasmid-deficient (A2497P(-)) organisms. Infection of human epithelial cells with either strain increased the expression of host genes coding for proinflammatory (granulocyte-macrophage colony-stimulating factor [GM-CSF], macrophage colony-stimulating factor [MCSF], interleukin-6 [IL-6], IL-8, IL-1α, CXCL1, CXCL2, CXCL3, intercellular adhesion molecule 1 [ICAM1]), chemoattraction (CCL20, CCL5, CXCL10), immune suppression (PD-L1, NFKB1B, TNFAIP3, CGB), apoptosis (CASP9, FAS, IL-24), and cell growth and fibrosis (EGR1 and IL-20) proteins. Statistically significant increases in the levels of expression of many of these genes were found in A2497-infected cells compared to the levels of expression in A2497P(-)-infected cells. Our findings suggest that the chlamydial plasmid plays a focal role in the host cell inflammatory response to infection and immune avoidance. These results provide new insights into the role of the chlamydial plasmid as a chlamydial virulence factor and its contributions to trachoma pathogenesis.
沙眼衣原体是一种专性细胞内寄生的嗜上皮性人类细菌病原体。眼部感染可导致沙眼，这是全球可预防失明的主要原因。致盲性沙眼的病理生理学是由结膜上皮细胞多次重复感染驱动的，会产生强烈的慢性炎症反应，导致粘膜下组织重塑和瘢痕形成。最近的报告显示，缺乏隐蔽性衣原体质粒的沙眼生物在猕猴眼中的感染力高度减弱，猕猴眼是人类沙眼感染的相关实验模型。为了更好地理解质粒介导的感染减弱的分子基础以及宿主免疫的潜在调节，我们对感染了携带沙眼衣原体质粒（A2497）和缺乏质粒（A2497P(-)）的生物的人类上皮细胞进行了转录谱分析。用这两种菌株感染人类上皮细胞均增加了编码促炎（粒细胞-巨噬细胞集落刺激因子[GM-CSF]、巨噬细胞集落刺激因子[MCSF]、白细胞介素-6[IL-6]、IL-8、IL-1α、CXCL1、CXCL2、CXCL3、细胞间粘附分子1[ICAM1]）、趋化作用（CCL20、CCL5、CXCL10）、免疫抑制（PD-L1、NFKB1B、TNFAIP3、CGB）、细胞凋亡（CASP9、FAS、IL-24）以及细胞生长和纤维化（EGR1和IL-20）蛋白的宿主基因的表达。与A2497P(-)感染细胞中的表达水平相比，在A2497感染的细胞中发现许多这些基因的表达水平有统计学上的显著增加。我们的研究结果表明，衣原体质粒在宿主细胞对感染的炎症反应和免疫逃避中起关键作用。这些结果为衣原体质粒作为衣原体毒力因子的作用及其对沙眼发病机制的贡献提供了新的见解。
