Mice Deficient in MyD88 Develop a Th2-Dominant Response and Severe Pathology in the Upper Genital Tract following Chlamydia muridarum Infection
Mice Deficient in MyD88 Develop a Th2-Dominant Response and Severe Pathology in the Upper Genital Tract following Chlamydia muridarum Infection
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DOI：
10.4049/jimmunol.0901593
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发表时间：
2010-03-01
影响因子：
4.4
通讯作者：
Zhong, Guangming
中科院分区：
文献类型：
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作者：
Chen, Lili;Lei, Lei;Zhong, Guangming
MyD88是许多天然免疫受体激活的信号通路所需的关键适配分子，在衣原体泌尿生殖道感染模型中进行了评估。与野生型小鼠相比，MyD88基因敲除(KO)小鼠在衣原体感染的第一周内未能在生殖道产生显著水平的炎性细胞因子。在衣原体感染后，MyD88 KO小鼠产生Th2显性免疫应答，而野生型小鼠产生Th1/Th17显性免疫应答。尽管早期炎性细胞因子的产生不足，缺乏Th1/Th17显性适应性免疫，但根据从阴道样本中提取的活体数量，MyD88 KO小鼠对衣原体阴道内感染的抵抗力似乎与野生型小鼠相同。然而，在MyD88 KO小鼠的上生殖道组织中检测到大量的衣原体。因此，MyD88 KO小鼠的上生殖道出现了更严重的病理变化。这些结果表明，MyD88依赖的信号通路不仅在衣原体感染宿主应答的早期阶段需要炎性细胞因子的产生，而且在Th1/Th17获得性免疫的发展中起着关键作用，这两者都可能是限制衣原体上行感染和减少上生殖道沙眼衣原体感染所必需的。免疫学杂志，2010,184：2602-2610。
MyD88, a key adaptor molecule required for many innate immunity receptor-activated signaling pathways, was evaluated in a Chlamydia muridarum urogenital tract infection model. Compared with wild-type mice, MyD88 knockout (KO) mice failed to produce significant levels of inflammatory cytokines in the genital tract during the first week of chlamydial infection. MyD88 KO mice developed a Th2-dominant whereas wild-type mice developed a Th1/Th17-dominant immune response after chlamydial infection. Despite the insufficient production of early inflammatory cytokines and lack of Th1/Th17-dominant adaptive immunity, MyD88 KO mice appeared to be as resistant to chlamydial intravaginal infection as wild-type mice based on the number of live organisms recovered from vaginal samples. However, significantly high numbers of chlamydial organisms were detected in the upper genital tract tissues of MyD88 KO mice. Consequently, MyD88 KO mice developed more severe pathology in the upper genital tract. These results together have demonstrated that MyD88-dependent-signaling pathway is not only required for inflammatory cytokine production in the early phase of host response to chlamydial infection but also plays a critical role in the development of Th1/Th17 adaptive immunity, both of which may be essential for limiting ascending infection and reducing pathology of the upper genital tract by chlamydial organisms. The Journal of Immunology, 2010, 184: 2602-2610.