Secretion of proinflammatory cytokines by epithelial cells in response to Chlamydia infection suggests a central role for epithelial cells in chlamydial pathogenesis
Secretion of proinflammatory cytokines by epithelial cells in response to Chlamydia infection suggests a central role for epithelial cells in chlamydial pathogenesis
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DOI：
10.1172/jci119136
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发表时间：
1997-01-01
影响因子：
15.9
通讯作者：
Kagnoff, MF
中科院分区：
文献类型：
--
作者：
Rasmussen, SJ;Eckmann, L;Kagnoff, MF
衣原体感染粘膜表面的上皮细胞，是性传播疾病的主要原因。感染的特点是炎症，在再次感染时会加剧，最终导致组织损伤和疤痕形成。虽然对疾病表现的发展至关重要，但人们对启动和维持对衣原体的炎症反应的机制知之甚少。沙眼衣原体和鹦鹉热衣原体感染宫颈和结肠上皮细胞可上调促炎症细胞因子IL-8、Groα、GM-CSF和IL-6的mRNA表达和分泌。与其他侵袭性细菌感染后快速但短暂的细胞因子诱导相反，上皮性细胞因子对衣原体的反应延迟到感染后20-24小时，并持续到衣原体的整个生长周期(2-4天)，需要细菌蛋白质合成。此外，衣原体感染后宫颈上皮细胞株和原代宫颈上皮细胞释放IL-1α，抗IL-1α可抑制促炎症细胞因子的分泌。这表明，受感染的上皮细胞溶解后释放的IL-1α可能通过刺激未感染的邻近细胞产生额外的细胞因子来放大炎症反应。这些发现提示了一种新的病理生理学概念，即粘膜表面对衣原体的急性宿主反应主要由上皮细胞启动和维持，上皮细胞是衣原体感染的第一和主要目标。
Chlamydia species infect epithelial cells at mucosal surfaces, and are major causes of sexually transmitted diseases. Infection is characterized by inflammation which is exacerbated upon reinfection, ultimately leading to tissue damage and scarring. Although central for the development of disease manifestations, little is known about the mechanisms that initiate and sustain the inflammatory response to Chlamydia. Infection of cervical and colonic epithelial cells with Chlamydia trachomatis and Chlamydia psittaci is shown in the present studies to upregulate mRNA expression and secretion of the proinflammatory cytokines IL-8, GRO alpha, GM-CSF, and IL-6. In contrast to the rapid, but transient, cytokine induction following infection with other invasive bacteria, the epithelial cytokine response to Chlamydia was delayed until 20-24 h after infection, persisted throughout the chlamydial growth cycle (2-4 d), and required bacterial protein synthesis. Moreover, epithelial cell lines and primary endocervical epithelial cells released IL-1 alpha after Chlamydia infection, and increased secretion of the proinflammatory cytokines could be inhibited by anti-IL-1 alpha. This suggests that IL-1 alpha, released following lysis of infected epithelial cells, may amplify the inflammatory response by stimulating additional cytokine production by noninfected neighboring cells. These findings suggest a novel pathophysiologic concept wherein the acute host response to Chlamydia at mucosal surfaces is primarily initiated and sustained by epithelial cells, the first and major targets of chlamydial infection.