{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T02:10:17Z","timestamp":1775614217173,"version":"3.50.1"},"reference-count":76,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2018,4,19]],"date-time":"2018-04-19T00:00:00Z","timestamp":1524096000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["INST 89\/291\u20101 FUGG"],"award-info":[{"award-number":["INST 89\/291\u20101 FUGG"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Rep Immunol"],"published-print":{"date-parts":[[2018,7]]},"abstract":"<jats:sec><jats:title>Problem<\/jats:title><jats:p>Neonatal sepsis is a serious threat especially for preterm infants. As existing in vitro and in vivo models have limitations, we generated a novel neonatal sepsis model using humanized mice and tested the effect of Betamethasone and Indomethacin which are used in the clinic in case of premature birth.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method of study<\/jats:title><jats:p>Humanized mice were infected with <jats:italic>Escherichia coli (E. coli)<\/jats:italic>. Subsequently, the effect of the infection itself, and treatment with Betamethasone and Indomethacin on survival, recovery, bacterial burden, leukocyte populations, and cytokine production, was analyzed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The human immune system in the animals responded with leukocyte trafficking to the site of infection and granulopoiesis in the bone marrow. Treatment with Indomethacin had no pronounced effect on the immune system or bacterial burden. Betamethasone induced a decline of splenocytes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The human immune system in humanized mice responds to the infection, making them a suitable model to study neonatal <jats:italic>E. coli<\/jats:italic> sepsis and the immune response of the neonatal immune system. Treatment with Betamethasone could have potential negative long\u2010term effects for the immune system of the child.<\/jats:p><\/jats:sec>","DOI":"10.1111\/aji.12859","type":"journal-article","created":{"date-parts":[[2018,4,19]],"date-time":"2018-04-19T16:24:33Z","timestamp":1524155073000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["A novel model to study neonatal <i>Escherichia coli<\/i> sepsis and the effect of treatment on the human immune system using humanized mice"],"prefix":"10.1111","volume":"80","author":[{"given":"Florian","family":"Schlieckau","sequence":"first","affiliation":[{"name":"Clinic of Gynecology and Obstetrics St. Hedwig University of Regensburg  Regensburg Germany"},{"name":"Institute of Immunology University of Regensburg  Regensburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela","family":"Schulz","sequence":"additional","affiliation":[{"name":"Clinic of Gynecology and Obstetrics St. Hedwig University of Regensburg  Regensburg Germany"},{"name":"Institute of Immunology University of Regensburg  Regensburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Fill Malfertheiner","sequence":"additional","affiliation":[{"name":"Clinic of Gynecology and Obstetrics St. Hedwig University of Regensburg  Regensburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathrin","family":"Entleutner","sequence":"additional","affiliation":[{"name":"Clinic of Gynecology and Obstetrics St. Hedwig University of Regensburg  Regensburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Birgit","family":"Seelbach\u2010Goebel","sequence":"additional","affiliation":[{"name":"Clinic of Gynecology and Obstetrics St. Hedwig University of Regensburg  Regensburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3129-9709","authenticated-orcid":false,"given":"Wolfgang","family":"Ernst","sequence":"additional","affiliation":[{"name":"Clinic of Gynecology and Obstetrics St. Hedwig University of Regensburg  Regensburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,4,19]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00031-13"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.4161\/viru.26906"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pcl.2012.12.003"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/INF.0b013e318223bad2"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2007-2171"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)60560-1"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1586\/1744666X.2014.942288"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1385\/IR:22:2-3:177"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0264-410X(01)00028-7"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri1394"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.70.12.6583-6588.2002"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.3109\/08830181003792803"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2075"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.earlhumdev.2016.05.016"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/753752"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cimid.2016.08.006"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1202810"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.26159"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humimm.2012.01.006"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2858"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01235-12"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.siny.2011.09.001"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/133.5.1668S"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1097\/00024382-200404000-00007"},{"key":"e_1_2_7_26_1","first-page":"246","volume-title":"Infectious diseases of the fetus and newborn infant","author":"Wilson C","year":"2011"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1677\/joe.0.0450515"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9378(94)90089-2"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2007.04.004"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2004.11.063"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.3345\/kjp.2010.53.12.989"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2007.07.033"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clp.2009.12.003"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00574"},{"key":"e_1_2_7_35_1","first-page":"e52018","article-title":"Non\u2010invasive model of neuropathogenic Escherichia coli infection in the neonatal rat","volume":"29","author":"Dalgakiran F","year":"2014","journal-title":"J Vis Exp"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.48.5.1503-1508.2004"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20092265"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/507423a"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/embor.2008.142"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1097\/00003246-199707000-00001"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.CCM.0000105581.01815.C6"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0b013e3181922bd3"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.5.2731"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.1041090103"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3660"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000461"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2012.08.005"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3070"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1159\/000296507"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2016.03.014"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1615\/CritRevImmunol.2016017098"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1590\/S0074-02762005000900024"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.67.1.206-212.1999"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0509307"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00491"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diagmicrobio.2012.12.011"},{"key":"e_1_2_7_57_1","first-page":"179","article-title":"Interleukin\u20106 as diagnostic marker for neonatal sepsis: determination of Access IL\u20106 cutoff for newborns","volume":"54","author":"Prinsen JH","year":"2008","journal-title":"Clin Lab"},{"key":"e_1_2_7_58_1","first-page":"FC15","article-title":"Betamethasone administration in pregnancy on maternal and newborn parameters","volume":"11","author":"Gaur K","year":"2017","journal-title":"J Clin Diagn Res"},{"key":"e_1_2_7_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0020-7292(97)00085-4"},{"key":"e_1_2_7_60_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1479-828X.1998.tb03095.x"},{"key":"e_1_2_7_61_1","doi-asserted-by":"publisher","DOI":"10.1515\/JPM.2002.041"},{"key":"e_1_2_7_62_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4401456"},{"key":"e_1_2_7_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0079-6123(10)82001-1"},{"key":"e_1_2_7_64_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.132.1.38"},{"key":"e_1_2_7_65_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-013-1069-2"},{"key":"e_1_2_7_66_1","doi-asserted-by":"publisher","DOI":"10.1136\/fn.79.2.F159a"},{"key":"e_1_2_7_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-5728(00)00406-9"},{"key":"e_1_2_7_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2013.03.009"},{"key":"e_1_2_7_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)66617-2"},{"key":"e_1_2_7_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9378(97)70609-4"},{"key":"e_1_2_7_71_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2003.043414"},{"key":"e_1_2_7_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2011.01.063"},{"key":"e_1_2_7_73_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1975.sp010992"},{"key":"e_1_2_7_74_1","first-page":"119","article-title":"Effect of indomethacin on the bone marrow and immune system of the mouse","volume":"7","author":"Boorman GA","year":"1982","journal-title":"J Clin Lab Immunol"},{"key":"e_1_2_7_75_1","doi-asserted-by":"crossref","first-page":"1820","DOI":"10.4049\/jimmunol.136.5.1820","article-title":"Chronic infection due to Mycobacterium intracellulare in mice: association with macrophage release of prostaglandin E2 and reversal by injection of indomethacin, muramyl dipeptide, or interferon\u2010gamma","volume":"136","author":"Edwards CK","year":"1986","journal-title":"J Immunol"},{"key":"e_1_2_7_76_1","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1542\/peds.70.3.343","article-title":"Improved survival in the suckling rat model of group B streptococcal sepsis after treatment with nonsteroidal anti\u2010inflammatory drugs","volume":"70","author":"Short BL","year":"1982","journal-title":"Pediatrics"},{"key":"e_1_2_7_77_1","doi-asserted-by":"publisher","DOI":"10.1515\/jpm-2014-0300"}],"container-title":["American Journal of Reproductive Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Faji.12859","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/aji.12859","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,23]],"date-time":"2023-09-23T04:20:22Z","timestamp":1695442822000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/aji.12859"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,4,19]]},"references-count":76,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2018,7]]}},"alternative-id":["10.1111\/aji.12859"],"URL":"https:\/\/doi.org\/10.1111\/aji.12859","archive":["Portico"],"relation":{},"ISSN":["1046-7408","1600-0897"],"issn-type":[{"value":"1046-7408","type":"print"},{"value":"1600-0897","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,4,19]]},"assertion":[{"value":"2017-12-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-03-27","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-04-19","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e12859"}}