{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T20:58:15Z","timestamp":1781643495132,"version":"3.54.5"},"reference-count":28,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,5,7]],"date-time":"2021-05-07T00:00:00Z","timestamp":1620345600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["1SC2HD086066-01A1"],"award-info":[{"award-number":["1SC2HD086066-01A1"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>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\u2212\/\u2212) 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\u2212\/\u2212 mice were unable to clear the infection compared to WT mice; also, miR-378b\u2212\/\u2212 mice exhibited a relatively higher Chlamydia burden throughout the duration of infection. However, gross pathology results showed that miR-378b\u2212\/\u2212 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\u2212\/\u2212 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.<\/jats:p>","DOI":"10.3390\/pathogens10050566","type":"journal-article","created":{"date-parts":[[2021,5,7]],"date-time":"2021-05-07T22:36:24Z","timestamp":1620426984000},"page":"566","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["MiR-378b Modulates Chlamydia-Induced Upper Genital Tract Pathology"],"prefix":"10.3390","volume":"10","author":[{"given":"Stephanie R.","family":"Lundy","sequence":"first","affiliation":[{"name":"Department of Microbiology, Biochemistry &amp; Immunology, Morehouse School of Medicine, Atlanta, GA 30310, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kobe","family":"Abney","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Biochemistry &amp; Immunology, Morehouse School of Medicine, Atlanta, GA 30310, USA"},{"name":"Department of Chemistry and Biochemistry, Spelman College, Atlanta, GA 30310, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debra","family":"Ellerson","sequence":"additional","affiliation":[{"name":"Centers for Disease Control &amp; Prevention (CDC), Atlanta, GA 30333, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7135-1260","authenticated-orcid":false,"given":"Joseph U.","family":"Igietseme","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Biochemistry &amp; Immunology, Morehouse School of Medicine, Atlanta, GA 30310, USA"},{"name":"Centers for Disease Control &amp; Prevention (CDC), Atlanta, GA 30333, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darin","family":"Carroll","sequence":"additional","affiliation":[{"name":"Centers for Disease Control &amp; Prevention (CDC), Atlanta, GA 30333, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francis O.","family":"Eko","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Biochemistry &amp; Immunology, Morehouse School of Medicine, Atlanta, GA 30310, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4759-6254","authenticated-orcid":false,"given":"Yusuf O.","family":"Omosun","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Biochemistry &amp; Immunology, Morehouse School of Medicine, Atlanta, GA 30310, USA"},{"name":"Centers for Disease Control &amp; Prevention (CDC), Atlanta, GA 30333, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"390","DOI":"10.15698\/mic2016.09.525","article-title":"Chlamydia trachomatis Genital Infections","volume":"3","author":"Ferone","year":"2016","journal-title":"Microb. Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1093\/humupd\/5.5.433","article-title":"Chlamydia trachomatis: Impact on human reproduction","volume":"5","author":"Paavonen","year":"1999","journal-title":"Hum. Reprod. Update"},{"key":"ref_3","unstructured":"(2021, May 06). Sexually Transmitted Infections (STIs) Are Very Common and Costly to the Nation\u2019s Health and Economy, Available online: https:\/\/www.cdc.gov\/std\/statistics\/prevalence-2020-at-a-glance.htm."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Smolarczyk, K., Mlynarczyk-Bonikowska, B., Rudnicka, E., Szukiewicz, D., Meczekalski, B., Smolarczyk, R., and Pieta, W. (2021). The Impact of Selected Bacterial Sexually Transmitted Diseases on Pregnancy and Female Fertility. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22042170"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Benyeogor, I., Simoneaux, T., Wu, Y., Lundy, S., George, Z., Ryans, K., McKeithen, D., Pais, R., Ellerson, D., and Lorenz, W.W. (2019). A unique insight into the MiRNA profile during genital chlamydial infection. BMC Genom., 20.","DOI":"10.1186\/s12864-019-5495-6"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1093\/infdis\/jit009","article-title":"Prevention of Chlamydia-Induced Infertility by Inhibition of Local Caspase Activity","volume":"207","author":"Igietseme","year":"2013","journal-title":"J. Infect. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Igietseme, J.U., Omosun, Y., Stuchlik, O., Reed, M.S., Partin, J., He, Q., Joseph, K., Ellerson, D., Bollweg, B., and George, Z. (2015). Role of Epithelial-Mesenchyme Transition in Chlamydia Pathogenesis. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0145198"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Yeruva, L., Myers, G.S., Spencer, N., Creasy, H.H., Adams, N.E., Maurelli, A.T., McChesney, G.R., Cleves, M.A., Ravel, J., and Bowlin, A. (2014). Early microRNA expression profile as a prognostic biomarker for the development of pelvic inflammatory disease in a mouse model of chlamydial genital infection. mBio, 5.","DOI":"10.1128\/mBio.01241-14"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1111\/aji.12281","article-title":"Chlamydia muridarumInfection Associated Host MicroRNAs in the Murine Genital Tract and Contribution to Generation of Host Immune Response","volume":"73","author":"Gupta","year":"2015","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1038\/nrg2936","article-title":"Gene silencing by microRNAs: Contributions of translational repression and mRNA decay","volume":"12","author":"Huntzinger","year":"2011","journal-title":"Nat. Rev. Genet."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1038\/nrm3838","article-title":"Regulation of microRNA biogenesis","volume":"15","author":"Ha","year":"2014","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Yeruva, L., Pouncey, D.L., Eledge, M.R., Bhattacharya, S., Luo, C., Weatherford, E.W., Ojcius, D.M., and Rank, R.G. (2016). MicroRNAs Modulate Pathogenesis Resulting from Chlamydial Infection in Mice. Infect. Immun., 85.","DOI":"10.1128\/IAI.00768-16"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3078","DOI":"10.3892\/or.2017.5939","article-title":"Regulation of UHRF1 by microRNA-378 modulates medulloblastoma cell proliferation and apoptosis","volume":"38","author":"Zhang","year":"2017","journal-title":"Oncol. Rep."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Wang, X.-L., Zhang, T., Wang, J., Zhang, D.-B., Zhao, F., Lin, X.-W., Wang, Z., Shi, P., and Pang, X.-N. (2015). miR-378b Promotes Differentiation of Keratinocytes through NKX3.1. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0136049"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.jhep.2018.08.026","article-title":"MicroRNA-378 promotes hepatic inflammation and fibrosis via modulation of the NF-\u03baB-TNF\u03b1 pathway","volume":"70","author":"Zhang","year":"2019","journal-title":"J. Hepatol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1042\/CS20160571","article-title":"miR-378 reduces mesangial hypertrophy and kidney tubular fibrosis via MAPK signalling","volume":"131","author":"Wang","year":"2017","journal-title":"Clin. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1186\/s13578-017-0161-7","article-title":"The roles of microRNA families in hepatic fibrosis","volume":"7","author":"Jiang","year":"2017","journal-title":"Cell Biosci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"10993","DOI":"10.1038\/ncomms10993","article-title":"MicroRNA-378 limits activation of hepatic stellate cells and liver fibrosis by suppressing Gli3 expression","volume":"7","author":"Hyun","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"625318","DOI":"10.3389\/fimmu.2021.625318","article-title":"Differential miRNA Profiles Correlate With Disparate Immunity Outcomes Associated With Vaccine Immunization and Chlamydial Infection","volume":"12","author":"Howard","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1186\/s12935-015-0192-2","article-title":"MicroRNA-378-5p suppresses cell proliferation and induces apoptosis in colorectal cancer cells by targeting BRAF","volume":"15","author":"Wang","year":"2015","journal-title":"Cancer Cell Int."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"S114","DOI":"10.1086\/652397","article-title":"Pathogenesis of Genital Tract Disease Due toChlamydia trachomatis","volume":"201","author":"Darville","year":"2010","journal-title":"J. Infect. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4029","DOI":"10.1128\/IAI.05535-11","article-title":"Enhanced Neutrophil Longevity and Recruitment Contribute to the Severity of Oviduct Pathology during Chlamydia muridarum Infection","volume":"79","author":"Frazer","year":"2011","journal-title":"Infect. Immun."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"4593","DOI":"10.1128\/IAI.00798-10","article-title":"The Chemokine Receptor CXCR2 Ligand KC (CXCL1) Mediates Neutrophil Recruitment and Is Critical for Development of Experimental Lyme Arthritis and Carditis","volume":"78","author":"Ritzman","year":"2010","journal-title":"Infect. Immun."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4930","DOI":"10.1182\/blood-2013-02-486217","article-title":"Mast cell and macrophage chemokines CXCL1\/CXCL2 control the early stage of neutrophil recruitment during tissue inflammation","volume":"121","author":"Dudeck","year":"2013","journal-title":"Blood"},{"key":"ref_25","first-page":"244","article-title":"Host inflammatory response and development of complications of Chlamydia trachomatis genital infection in CCR5-deficient mice and subfertile women with the CCR5delta32 gene deletion","volume":"38","author":"Barr","year":"2005","journal-title":"J. Microbiol. Immunol. Infect."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"873","DOI":"10.2174\/156652409789105570","article-title":"Hedgehog target genes: Mechanisms of carcinogenesis induced by aberrant hedgehog signaling activation","volume":"9","author":"Katoh","year":"2009","journal-title":"Curr. Mol. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"187","DOI":"10.3892\/ijo_00000328","article-title":"Integrative genomic analyses on GLI1: Positive regulation of GLI1 by Hedgehog-GLI, TGFbeta-Smads, and RTK-PI3K-AKT signals, and negative regulation of GLI1 by Notch-CSL-HES\/HEY, and GPCR-Gs-PKA signals","volume":"35","author":"Katoh","year":"2009","journal-title":"Int. J. Oncol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"11405","DOI":"10.1038\/s41598-019-47878-y","article-title":"Effect of Time of Day of Infection on Chlamydia Infectivity and Pathogenesis","volume":"9","author":"Lundy","year":"2019","journal-title":"Sci. Rep."}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/10\/5\/566\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:57:52Z","timestamp":1760162272000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/10\/5\/566"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,7]]},"references-count":28,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2021,5]]}},"alternative-id":["pathogens10050566"],"URL":"https:\/\/doi.org\/10.3390\/pathogens10050566","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,7]]}}}