MiR-378b Modulates Chlamydia-Induced Upper Genital Tract Pathology.
MiR-378b Modulates Chlamydia-Induced Upper Genital Tract Pathology.
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DOI：
10.3390/pathogens10050566
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发表时间：
2021-05-07
期刊：
影响因子：
--
通讯作者：
Omosun YO
中科院分区：
文献类型：
--
作者：
Lundy SR;Abney K;Ellerson D;Igietseme JU;Carroll D;Eko FO;Omosun YO
生殖道沙眼衣原体感染会导致严重的生殖病理，如输卵管炎和盆腔炎，可导致输卵管因素不孕。microRNAs（miRNAs）是哺乳动物发育、免疫和炎症及感染（包括衣原体感染）过程中基因表达的进化保守调节因子。在参与调节衣原体感染的宿主反应和病理结果的miRNA中，我们已经表明miR-378 b在初次感染和再感染期间显著差异表达。在这项研究中，我们检验了miR-378 b参与衣原体感染的病理结果的假设。我们使用Crispr/Cas开发了miR-378 b敲除小鼠（miR-378 b −/−），并使用衣原体感染它们沿着野生型（WT）对照，以比较感染性和生殖病理。结果显示，与WT小鼠相比，miR-378 b −/−小鼠无法清除感染;此外，miR-378 b −/−小鼠在整个感染期间表现出相对较高的衣原体负荷。然而，大体病理学结果显示，与WT小鼠相比，miR-378 b −/−小鼠在两次感染后的子宫扩张和病理学病变显著减少。此外，感染miR-378 b −/−小鼠的妊娠率和生育率显示出对衣原体诱导的不孕症的保护，生育率与未感染的WT小鼠相当。这些结果很有趣，因为它们表明miR-378 b在调节宿主免疫反应中很重要，这些免疫反应控制衣原体复制并驱动导致不孕症等并发症的炎症。这一发现对衣原体并发症的生物标志物和预防疾病的目标具有重要意义。
Genital Chlamydia trachomatis infection causes severe reproductive pathologies such as salpingitis and pelvic inflammatory disease that can lead to tubal factor infertility. MicroRNAs (miRNAs) are evolutionarily conserved regulators of mammalian gene expression in development, immunity and pathophysiologic processes during inflammation and infection, including Chlamydia infection. Among the miRNAs involved in regulating host responses and pathologic outcome of Chlamydia infection, we have shown that miR-378b was significantly differentially expressed during primary infection and reinfection. In this study, we tested the hypothesis that miR-378b is involved in the pathological outcome of Chlamydia infection. We developed miR-378b knockout mice (miR-378b−/−) using Crispr/Cas and infected them along with their wild-type (WT) control with Chlamydia to compare the infectivity and reproductive pathologies. The results showed that miR-378b−/− mice were unable to clear the infection compared to WT mice; also, miR-378b−/− mice exhibited a relatively higher Chlamydia burden throughout the duration of infection. However, gross pathology results showed that miR-378b−/− mice had significantly reduced uterine dilatations and pathologic lesions after two infections compared to WT mice. In addition, the pregnancy and fertility rates for infected miR-378b−/− mice showed protection from Chlamydia-induced infertility with fertility rate that was comparable to uninfected WT mice. These results are intriguing as they suggest that miR-378b is important in regulating host immune responses that control Chlamydial replication and drive the inflammation that causes complications such as infertility. The finding has important implications for biomarkers of Chlamydial complications and targets for prevention of disease.
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影响因子：
5.6
作者：
Smolarczyk K;Mlynarczyk-Bonikowska B;Rudnicka E;Szukiewicz D;Meczekalski B;Smolarczyk R;Pieta W
通讯作者：
Pieta W
影响因子：
5.8
作者：
Wang Z;Ma B;Ji X;Deng Y;Zhang T;Zhang X;Gao H;Sun H;Wu H;Chen X;Zhao R
通讯作者：
Zhao R
影响因子：
3.1
作者：
Frazer, Lauren C.;O'Connell, Catherine M.;Darville, Toni
通讯作者：
Darville, Toni
影响因子：
16.6
作者：
Hyun J;Wang S;Kim J;Rao KM;Park SY;Chung I;Ha CS;Kim SW;Yun YH;Jung Y
通讯作者：
Jung Y
早期microRNA表达谱是在衣原体生殖器感染的小鼠模型中发展骨盆炎症性疾病的预后生物标志物。
影响因子：
6.4
作者：
Yeruva L;Myers GS;Spencer N;Creasy HH;Adams NE;Maurelli AT;McChesney GR;Cleves MA;Ravel J;Bowlin A;Rank RG
通讯作者：
Rank RG