Life Science Department, Fresno City College, Fresno, CA, United States of America.
Department of Biomedical Sciences, Arthur Dugoni School of Dentistry, University of the Pacific, San Francisco, CA, United States of America.
PLoS One. 2020 Mar 25;15(3):e0230718. doi: 10.1371/journal.pone.0230718. eCollection 2020.
Chlamydia trachomatis is the most common bacterial sexually-transmitted infection and the major cause of preventable blindness worldwide. The asymptomatic nature of many infections along with uncontrolled inflammation leads to irreversible damage in the upper genital tract and the tarsal conjunctivae, with the major complications of infertility and chronic pelvic pain, and blindness, respectively. Inflammation must, therefore, be tightly regulated to avoid an unrestrained immune response. The genetic factors that regulate inflammation through Toll-like receptor (TLR) signaling pathways during C. trachomatis infection have not been fully characterized. SIGIRR (also known as IL-1R8 or TIR8) can regulate inflammation in response to various pathogens and diseases. However, nothing is known about its role during C. trachomatis infection. Expression of the pro-inflammatory chemokine, IL-8, was measured in epithelial cells infected with C. trachomatis. The effect of SIGIRR was determined by depleting SIGIRR or over-expressing SIGIRR in the epithelial cells before infection. Our results indicate that, in the absence of SIGIRR, epithelial cells induce higher levels of the pro-inflammatory chemokine, IL-8, in response to C. trachomatis infection. In addition, SIGIRR associates with MyD88 in both infected and uninfected infected cells. Collectively, our data demonstrate that SIGIRR functions as a negative regulator of the immune response to C. trachomatis infection. This finding provides insights into the immuno-pathogenesis of C. trachomatis that can be used to treat and identify individuals at risk of uncontrolled inflammation during infection.
沙眼衣原体是最常见的细菌性性传播感染病原体，也是全球可预防盲的主要病因。许多感染呈无症状，且炎症不受控制，这会导致上生殖道和跗骨结膜发生不可逆转的损伤，分别导致不孕、慢性盆腔痛和失明等主要并发症。因此，必须严格控制炎症，避免免疫反应失控。通过 Toll 样受体（TLR）信号通路调节炎症的遗传因素在沙眼衣原体感染过程中尚未得到充分描述。SIGIRR（也称为 IL-1R8 或 TIR8）可调节对各种病原体和疾病的炎症反应。然而，目前尚不清楚其在沙眼衣原体感染中的作用。测量了上皮细胞感染沙眼衣原体后促炎趋化因子 IL-8 的表达。通过在感染前耗尽上皮细胞中的 SIGIRR 或过表达 SIGIRR 来确定 SIGIRR 的作用。我们的结果表明，在没有 SIGIRR 的情况下，上皮细胞在感染沙眼衣原体时会诱导更高水平的促炎趋化因子 IL-8。此外，SIGIRR 在感染和未感染的细胞中均与 MyD88 相关。总之，我们的数据表明 SIGIRR 是沙眼衣原体感染免疫反应的负调节剂。这一发现为沙眼衣原体的免疫发病机制提供了新的见解，可用于治疗和识别感染期间炎症不受控制的个体。
