Localization of TLR2 and MyD88 to Chlamydia trachomatis inclusions -: Evidence for signaling by intracellular TLR2 during infection with an obligate intracellular pathogen
Localization of TLR2 and MyD88 to Chlamydia trachomatis inclusions -: Evidence for signaling by intracellular TLR2 during infection with an obligate intracellular pathogen
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DOI：
10.1074/jbc.m510182200
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发表时间：
2006-01-20
影响因子：
4.8
通讯作者：
Ingalls, RR
中科院分区：
文献类型：
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作者：
O'Connell, CM;Ionova, IA;Ingalls, RR
沙眼衣原体是一种专性细胞内革兰氏阴性病原体，也是重要眼部和生殖道疾病的病原体。衣原体主要感染上皮细胞，这些细胞对感染的炎症反应指导先天性和适应性免疫反应。本研究的重点是确定参与沙眼衣原体 L2 血清型感染后早期事件的细胞免疫受体。我们发现显性失活的 MyD88 在衣原体感染过程中抑制白细胞介素 8 (IL-8) 的分泌。此外，受感染细胞分泌IL-8需要Toll样受体(TLR)-2的表达，而TLR4/MD-2表达的影响很小。细胞活化依赖于活的复制细菌的感染，因为紫外线照射的细菌的感染以及用氯霉素而非氨苄青霉素处理感染的细胞会消除IL-8分泌的诱导。最后，我们发现 TLR2 和 MyD88 与细胞内衣原体包涵体共定位，表明 TLR2 积极参与来自该细胞内位置的信号传导。这些数据支持 TLR2 在宿主对沙眼衣原体感染的反应中的作用。我们的数据进一步证明，在衣原体感染过程中，TLR2 和接头 MyD88 被特异性地募集到细菌或包涵体膜上，并提供了第一个证据，证明细胞内 TLR2 在细胞内细菌感染过程中负责信号转导。
Chlamydia trachomatis is an obligate intracellular Gram-negative pathogen and the etiologic agent of significant ocular and genital tract diseases. Chlamydiae primarily infect epithelial cells, and the inflammatory response of these cells to the infection directs both the innate and adaptive immune response. This study focused on determining the cellular immune receptors involved in the early events following infection with the L2 serovar of C. trachomatis. We found that dominant negative MyD88 inhibited interleukin-8 (IL-8) secretion during a productive infection with chlamydia. Furthermore, expression of Toll-like receptor (TLR)-2 was required for IL-8 secretion from infected cells, whereas the effect of TLR4/MD-2 expression was minimal. Cell activation was dependent on infection with live, replicating bacteria, because infection with UV-irradiated bacteria and treatment of infected cells with chloramphenicol, but not ampicillin, abrogated the induction of IL-8 secretion. Finally, we show that both TLR2 and MyD88 co-localize with the intracellular chlamydial inclusion, suggesting that TLR2 is actively engaged in signaling from this intracellular location. These data support the role of TLR2 in the host response to infection with C. trachomatis. Our data further demonstrate that TLR2 and the adaptor MyD88 are specifically recruited to the bacterial or inclusion membrane during a productive infection with chlamydia and provide the first evidence that intracellular TLR2 is responsible for signal transduction during infection with an intracellular bacterium.