MiR-378b Modulates <i>Chlamydia</i>-Induced Upper Genital Tract Pathology
Genital <i>Chlamydia trachomatis</i> 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, imm...
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| Format: | Article |
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MDPI AG
2021-05-01
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| Series: | Pathogens |
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| Online Access: | https://www.mdpi.com/2076-0817/10/5/566 |
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| author | Stephanie R. Lundy Kobe Abney Debra Ellerson Joseph U. Igietseme Darin Carroll Francis O. Eko Yusuf O. Omosun |
| author_facet | Stephanie R. Lundy Kobe Abney Debra Ellerson Joseph U. Igietseme Darin Carroll Francis O. Eko Yusuf O. Omosun |
| author_sort | Stephanie R. Lundy |
| collection | DOAJ |
| description | Genital <i>Chlamydia trachomatis</i> 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 <i>Chlamydia</i> infection. Among the miRNAs involved in regulating host responses and pathologic outcome of <i>Chlamydia</i> 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 <i>Chlamydia</i> infection. We developed miR-378b knockout mice (miR-378b<sup>−/−</sup>) using Crispr/Cas and infected them along with their wild-type (WT) control with <i>Chlamydia</i> to compare the infectivity and reproductive pathologies. The results showed that miR-378b<sup>−/−</sup> mice were unable to clear the infection compared to WT mice; also, miR-378b<sup>−/−</sup> mice exhibited a relatively higher <i>Chlamydia</i> burden throughout the duration of infection. However, gross pathology results showed that miR-378b<sup>−/−</sup> 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<sup>−/−</sup> mice showed protection from <i>Chlamydia</i>-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. |
| first_indexed | 2024-03-10T11:38:40Z |
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| issn | 2076-0817 |
| language | English |
| last_indexed | 2024-03-10T11:38:40Z |
| publishDate | 2021-05-01 |
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| record_format | Article |
| series | Pathogens |
| spelling | doaj.art-8222fde3acbe4fa7a9da2b83b44e72832023-11-21T18:39:30ZengMDPI AGPathogens2076-08172021-05-0110556610.3390/pathogens10050566MiR-378b Modulates <i>Chlamydia</i>-Induced Upper Genital Tract PathologyStephanie R. Lundy0Kobe Abney1Debra Ellerson2Joseph U. Igietseme3Darin Carroll4Francis O. Eko5Yusuf O. Omosun6Department of Microbiology, Biochemistry & Immunology, Morehouse School of Medicine, Atlanta, GA 30310, USADepartment of Microbiology, Biochemistry & Immunology, Morehouse School of Medicine, Atlanta, GA 30310, USACenters for Disease Control & Prevention (CDC), Atlanta, GA 30333, USADepartment of Microbiology, Biochemistry & Immunology, Morehouse School of Medicine, Atlanta, GA 30310, USACenters for Disease Control & Prevention (CDC), Atlanta, GA 30333, USADepartment of Microbiology, Biochemistry & Immunology, Morehouse School of Medicine, Atlanta, GA 30310, USADepartment of Microbiology, Biochemistry & Immunology, Morehouse School of Medicine, Atlanta, GA 30310, USAGenital <i>Chlamydia trachomatis</i> 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 <i>Chlamydia</i> infection. Among the miRNAs involved in regulating host responses and pathologic outcome of <i>Chlamydia</i> 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 <i>Chlamydia</i> infection. We developed miR-378b knockout mice (miR-378b<sup>−/−</sup>) using Crispr/Cas and infected them along with their wild-type (WT) control with <i>Chlamydia</i> to compare the infectivity and reproductive pathologies. The results showed that miR-378b<sup>−/−</sup> mice were unable to clear the infection compared to WT mice; also, miR-378b<sup>−/−</sup> mice exhibited a relatively higher <i>Chlamydia</i> burden throughout the duration of infection. However, gross pathology results showed that miR-378b<sup>−/−</sup> 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<sup>−/−</sup> mice showed protection from <i>Chlamydia</i>-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.https://www.mdpi.com/2076-0817/10/5/566miR-378b<sup>−/−</sup> miceChlamydial pathogenesis<i>Chlamydia muridarum</i>infertility |
| spellingShingle | Stephanie R. Lundy Kobe Abney Debra Ellerson Joseph U. Igietseme Darin Carroll Francis O. Eko Yusuf O. Omosun MiR-378b Modulates <i>Chlamydia</i>-Induced Upper Genital Tract Pathology Pathogens miR-378b<sup>−/−</sup> mice Chlamydial pathogenesis <i>Chlamydia muridarum</i> infertility |
| title | MiR-378b Modulates <i>Chlamydia</i>-Induced Upper Genital Tract Pathology |
| title_full | MiR-378b Modulates <i>Chlamydia</i>-Induced Upper Genital Tract Pathology |
| title_fullStr | MiR-378b Modulates <i>Chlamydia</i>-Induced Upper Genital Tract Pathology |
| title_full_unstemmed | MiR-378b Modulates <i>Chlamydia</i>-Induced Upper Genital Tract Pathology |
| title_short | MiR-378b Modulates <i>Chlamydia</i>-Induced Upper Genital Tract Pathology |
| title_sort | mir 378b modulates i chlamydia i induced upper genital tract pathology |
| topic | miR-378b<sup>−/−</sup> mice Chlamydial pathogenesis <i>Chlamydia muridarum</i> infertility |
| url | https://www.mdpi.com/2076-0817/10/5/566 |
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