Signaling via Tumor Necrosis Factor Receptor 1 but Not Toll-Like Receptor 2 Contributes Significantly to Hydrosalpinx Development following Chlamydia muridarum Infection
Signaling via Tumor Necrosis Factor Receptor 1 but Not Toll-Like Receptor 2 Contributes Significantly to Hydrosalpinx Development following Chlamydia muridarum Infection
复制标题
DOI：
10.1128/iai.01668-13
复制
发表时间：
2014-05-01
影响因子：
3.1
通讯作者：
Zhong, Guangming
中科院分区：
文献类型：
--
作者：
Dong, Xiaohua;Liu, Yuanjun;Zhong, Guangming
下生殖道衣原体感染可导致输卵管积水，并伴有模式识别受体tlr2和炎症细胞因子受体tnfr1介导的信号通路的激活。在目前的研究中，我们比较了这两种受体在衣原体诱导小鼠输卵管积水中的相对作用。我们发现TLR2或TNFR1缺失或不缺失的小鼠从阴道拭子中脱落的活生物体的时间过程相似，这表明这些受体介导的信号通路不是控制衣原体下生殖器感染所必需的。然而，缺乏TNFR1而不缺乏TLR2的小鼠输卵管积水明显减少。致病性的降低与体外再刺激tnfr1缺陷小鼠的脾细胞中白细胞介素-17的显著减少有关。尽管TLR2缺陷小鼠出现的输卵管积水与野生型小鼠一样严重，但来自TLR2缺陷小鼠而非TNFR1缺陷小鼠的腹腔巨噬细胞在衣原体刺激下产生的细胞因子显著减少，这表明巨噬细胞对衣原体感染反应的减少并不总是导致输卵管积水的减少。因此，我们证明了细胞因子受体TNFR1触发的信号通路在衣原体诱导输卵管积水中比模式识别受体TLR2介导的信号通路发挥更显著的作用，为进一步揭示衣原体致病机制奠定了基础。
Chlamydial infection in the lower genital tract can lead to hydrosalpinx, which is accompanied by activation of both pattern recognition receptor TLR2-and inflammatory cytokine receptor TNFR1-mediated signaling pathways. In the current study, we compared the relative contributions of these two receptors to chlamydial induction of hydrosalpinx in mice. We found that mice with or without deficiencies in TLR2 or TNFR1 displayed similar time courses of live organism shedding from vaginal swabs, suggesting that these receptor-mediated signaling pathways are not required for controlling chlamydial lower genital infection. However, mice deficient in TNFR1 but not TLR2 developed significantly reduced hydrosalpinx. The decreased pathogenicity correlated with a significant reduction in interleukin-17 by in vitro-restimulated splenocytes of TNFR1-deficient mice. Although TLR2-deficient mice developed hydrosalpinx as severe as that of wild-type mice, peritoneal macrophages from mice deficient in TLR2 but not TNFR1 produced significantly reduced cytokines upon chlamydial stimulation, suggesting that reduced macrophage responses to chlamydial infection do not always lead to a reduction in hydrosalpinx. Thus, we have demonstrated that the signaling pathways triggered by the cytokine receptor TNFR1 play a more significant role in chlamydial induction of hydrosalpinx than those mediated by the pattern recognition receptor TLR2, which has laid a foundation for further revealing the chlamydial pathogenic mechanisms.