{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T21:25:25Z","timestamp":1792185925050,"version":"4.4.0"},"reference-count":69,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2017,3,1]],"date-time":"2017-03-01T00:00:00Z","timestamp":1488326400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2017,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Colonization of the endometrium by pathogenic bacteria ascending from the lower female reproductive tract (FRT) is associated with many gynecologic and obstetric health complications. To study these host-microbe interactions\n            <jats:italic>in vitro<\/jats:italic>\n            , we developed a human three-dimensional (3-D) endometrial epithelial cell (EEC) model using the HEC-1A cell line and the rotating wall vessel (RWV) bioreactor technology. Our model, composed of 3-D EEC aggregates, recapitulates several functional\/structural characteristics of human endometrial epithelial tissue, including cell differentiation, the presence of junctional complexes\/desmosomes and microvilli, and the production of membrane-associated mucins and Toll-like receptors (TLRs). TLR function was evaluated by exposing the EEC aggregates to viral and bacterial products. Treatment with poly(I\u00b7C) and flagellin but not with synthetic lipoprotein (fibroblast-stimulating lipoprotein 1 [FSL-1]) or lipopolysaccharide (LPS) significantly induced proinflammatory mediators in a dose-dependent manner. To simulate ascending infection, we infected EEC aggregates with commensal and pathogenic bacteria:\n            <jats:named-content content-type=\"genus-species\">Lactobacillus crispatus<\/jats:named-content>\n            ,\n            <jats:named-content content-type=\"genus-species\">Gardnerella vaginalis<\/jats:named-content>\n            , and\n            <jats:named-content content-type=\"genus-species\">Neisseria gonorrhoeae<\/jats:named-content>\n            . All vaginal microbiota and\n            <jats:named-content content-type=\"genus-species\">N. gonorrhoeae<\/jats:named-content>\n            efficiently colonized the 3-D surface, localizing to crevices of the EEC model and interacting with multiple adjacent cells simultaneously. However, only infection with pathogenic\n            <jats:named-content content-type=\"genus-species\">N. gonorrhoeae<\/jats:named-content>\n            and not infection with the other bacteria tested significantly induced proinflammatory mediators and significant ultrastructural changes to the host cells. The latter observation is consistent with clinical findings and illustrated the functional specificity of our system. Additionally, we highlighted the utility of the 3-D EEC model for the study of the pathogenesis of\n            <jats:named-content content-type=\"genus-species\">N. gonorrhoeae<\/jats:named-content>\n            using a well-characterized \u0394\n            <jats:italic>pilT<\/jats:italic>\n            mutant. Overall, this study demonstrates that the human 3-D EEC model is a robust tool for studying host-microbe interactions and bacterial pathogenesis in the upper FRT.\n          <\/jats:p>","DOI":"10.1128\/iai.01049-16","type":"journal-article","created":{"date-parts":[[2017,1,5]],"date-time":"2017-01-05T02:30:44Z","timestamp":1483583444000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":64,"title":["Human Three-Dimensional Endometrial Epithelial Cell Model To Study Host Interactions with Vaginal Bacteria and Neisseria gonorrhoeae"],"prefix":"10.1128","volume":"85","author":[{"given":"Pawe\u0142","family":"\u0141aniewski","sequence":"first","affiliation":[{"name":"Department of Basic Medical Sciences, College of Medicine\u2014Phoenix, University of Arizona, Phoenix, Arizona, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana","family":"Gomez","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences, College of Medicine\u2014Phoenix, University of Arizona, Phoenix, Arizona, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geoffrey","family":"Hire","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences, College of Medicine\u2014Phoenix, University of Arizona, Phoenix, Arizona, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8301-0674","authenticated-orcid":false,"given":"Magdalene","family":"So","sequence":"additional","affiliation":[{"name":"Department of Immunobiology and BIO5 Institute, College of Medicine\u2014Tucson, University of Arizona, Tucson, Arizona, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8540-5917","authenticated-orcid":false,"given":"Melissa M.","family":"Herbst-Kralovetz","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences, College of Medicine\u2014Phoenix, University of Arizona, Phoenix, Arizona, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","first-page":"1737","article-title":"Association between bacterial vaginosis and preterm delivery of a low-birth-weight infant","volume":"333","author":"Hillier SL","year":"1995","unstructured":"Hillier SL Nugent RP Eschenbach DA Krohn MA Gibbs RS Martin DH Cotch MF Edelman R Pastorek JG II Rao AV McNellis D Regan JA Carey C Klebanoff M . 1995. Association between bacterial vaginosis and preterm delivery of a low-birth-weight infant. The Vaginal Infections and Prematurity Study Group. N Engl J Med333:1737\u20131742.","journal-title":"The Vaginal Infections and Prematurity Study Group"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1097\/OLQ.0b013e31827c5a5b"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2007.01.035"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-021115-105238"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2015.05.032"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2015.09.053"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3008599"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10815-015-0614-z"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.7717\/peerj.1602"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jri.2010.07.002"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmu065"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1186\/1477-7827-8-113"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1111\/aogs.12296"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa043802"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiw121"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiu089"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiw159"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2014.11.043"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0053997"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2011.05.031"},{"key":"e_1_3_2_22_2","first-page":"456","article-title":"Lower genital tract infection and endometritis: insight into subclinical pelvic inflammatory disease","volume":"100","author":"Wiesenfeld HC","year":"2002","unstructured":"Wiesenfeld HC Hillier SL Krohn MA Amortegui AJ Heine RP Landers DV Sweet RL . 2002. Lower genital tract infection and endometritis: insight into subclinical pelvic inflammatory disease. Obstet Gynecol100:456\u2013463.","journal-title":"Obstet Gynecol"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.3181\/00379727-202-43525"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2423"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiw130"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1858"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.00503"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbiomolbio.2008.02.005"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.3791\/3868"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9378(72)90861-7"},{"key":"e_1_3_2_31_2","volume-title":"Human female reproductive tract: a scanning electron microscopy atlas","author":"Ludwig H","year":"1979","unstructured":"Ludwig H Metzger H . 1979. Human female reproductive tract: a scanning electron microscopy atlas. Springer-Verlag, New York, NY."},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/del388"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2567.2004.01898.x"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0033-1361822"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00687-07"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.109.080408"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.112.103366"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.12.4.517"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(03)01134-3"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2003.06.002"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deh722"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2012.06.017"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deh775"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2006.04.044"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0897.2007.00566.x"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod56.4.999"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-15856-3_4"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/del189"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.pgp.0000225837.32719.c1"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deu146"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.25213"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2012.12.012"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2015.11.025"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M304558200"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6603003"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1136\/sextrans-2015-052285"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1086\/423963"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.67.7.3469-3480.1999"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2011.01607.x"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1111\/cmi.12153"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.83.7.2177"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1038\/35024105"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.1998.00935.x"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jit101"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.188.2.373"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-1759(01)00489-6"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.1001\/archsurg.1993.01420140035006"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiu004"},{"key":"e_1_3_2_69_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2008.73"},{"key":"e_1_3_2_70_2","doi-asserted-by":"publisher","DOI":"10.1093\/molehr\/gar064"}],"container-title":["Infection and Immunity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/IAI.01049-16","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/IAI.01049-16","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,5]],"date-time":"2022-03-05T10:39:43Z","timestamp":1646476783000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/IAI.01049-16"}},"subtitle":[],"editor":[{"given":"Andreas J.","family":"B\u00e4umler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2017,3]]},"references-count":69,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2017,3]]}},"alternative-id":["10.1128\/IAI.01049-16"],"URL":"https:\/\/doi.org\/10.1128\/iai.01049-16","relation":{},"ISSN":["0019-9567","1098-5522"],"issn-type":[{"value":"0019-9567","type":"print"},{"value":"1098-5522","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,3]]},"assertion":[{"value":"2016-12-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-12-23","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-02-23","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01049-16"}}