Lundy Stephanie R, Abney Kobe, Ellerson Debra, Igietseme Joseph U, Carroll Darin, Eko Francis O, Omosun Yusuf O
Department of Microbiology, Biochemistry & Immunology, Morehouse School of Medicine, Atlanta, GA 30310, USA.
Department of Chemistry and Biochemistry, Spelman College, Atlanta, GA 30310, USA.
Pathogens. 2021 May 7;10(5):566. doi: 10.3390/pathogens10050566.
Genital 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 infection. Among the miRNAs involved in regulating host responses and pathologic outcome of 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 infection. We developed miR-378b knockout mice (miR-378b) using Crispr/Cas and infected them along with their wild-type (WT) control with 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 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 -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.
生殖道感染会引发严重的生殖系统病变，如输卵管炎和盆腔炎，进而导致输卵管因素不孕症。微小RNA（miRNA）是哺乳动物基因表达在发育、免疫以及炎症和感染（包括衣原体感染）病理生理过程中的进化保守调节因子。在参与调节宿主对衣原体感染反应及病理结果的miRNA中，我们已表明miR-378b在初次感染和再次感染期间存在显著差异表达。在本研究中，我们验证了miR-378b参与衣原体感染病理结果的假说。我们利用Crispr/Cas技术构建了miR-378b基因敲除小鼠（miR-378b -/-），并将其与野生型（WT）对照小鼠一起感染衣原体，以比较感染性和生殖系统病变情况。结果显示，与WT小鼠相比，miR-378b -/-小鼠无法清除感染；此外，在整个感染期间，miR-378b -/-小鼠体内的衣原体负荷相对更高。然而，大体病理学结果表明，与WT小鼠相比，miR-378b -/-小鼠在两次感染后子宫扩张和病理损伤明显减轻。此外，感染后的miR-378b -/-小鼠的妊娠率和生育率显示出对衣原体诱导不孕症的保护作用，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-378b在调节宿主免疫反应中很重要，这种免疫反应可控制衣原体复制并引发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及疾病预防靶点具有重要意义。
