Department of Pediatrics, University of North Carolina, University of North Carolina, Chapel Hill, North Carolina, USA.
Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
J Infect Dis. 2021 Aug 16;224(12 Suppl 2):S47-S55. doi: 10.1093/infdis/jiab168.
Chlamydia trachomatis-genital infection in women can be modeled in mice using Chlamydia muridarum. Using this model, it has been shown that the cytokines tumor necrosis factor (TNF)α and interleukin (IL)-1α lead to irreversible tissue damage in the oviducts. In this study, we investigated the contribution of TNFα on IL-1α synthesis in infected epithelial cells. We show that C muridarum infection enhanced TNFα-induced IL-1α expression and release in a mouse epithelial cell line. In addition to IL-1α, several TNFα-induced inflammatory genes were also highly induced, and infection enhanced TNF-induced cell death. In the mouse model of genital infection, oviducts from mice lacking the TNFα receptor displayed minimal staining for IL-1α compared with wild-type oviducts. Our results suggest TNFα and IL-1α enhance each other's downstream effects resulting in a hyperinflammatory response to chlamydial infection. We propose that biologics targeting TNF-induced IL-1α synthesis could be used to mitigate tissue damage during chlamydial infection.
沙眼衣原体-生殖道感染可在小鼠中使用鼠型沙眼衣原体进行建模。利用该模型，已经证明细胞因子肿瘤坏死因子 (TNF)α 和白细胞介素 (IL)-1α 导致输卵管的不可逆转的组织损伤。在这项研究中，我们研究了 TNFα 对感染上皮细胞中 IL-1α 合成的贡献。我们发现，C 型沙眼衣原体感染增强了 TNFα 诱导的小鼠上皮细胞系中 IL-1α 的表达和释放。除了 IL-1α 之外，几种 TNFα 诱导的炎症基因也被高度诱导，并且感染增强了 TNF 诱导的细胞死亡。在生殖道感染的小鼠模型中，与野生型输卵管相比，缺乏 TNFα 受体的小鼠的输卵管中 IL-1α 的染色最小。我们的结果表明，TNFα 和 IL-1α 增强彼此的下游效应，导致对衣原体感染的过度炎症反应。我们提出，针对 TNF 诱导的 IL-1α 合成的生物制剂可用于减轻衣原体感染期间的组织损伤。
