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While BCG is generally safe for full\u2010term infants, its application in preterm infants is contentious due to their immature immune systems and heightened susceptibility to adverse effects. Preterm infants, particularly those with low birth weight, are at an elevated risk of severe complications, such as necrotizing enterocolitis (NEC), a life\u2010threatening inflammatory condition of the intestines. NEC is characterised by dysregulated immune responses to microbial colonisation, with myeloid\u2010derived suppressor cells (MDSCs) playing a crucial role in maintaining immune tolerance during early life. This study reveals that BCG vaccination significantly exacerbates NEC severity (<jats:italic>p<\/jats:italic>\u2009=\u20090.0048) by enhancing glycolysis and upregulating mTOR\u2010HIF1\u03b1 signalling in neonatal monocytic MDSCs (M\u2010MDSCs), thereby impairing their immunosuppressive function. Pharmacological or genetic inhibition of mTOR\u2010HIF1\u03b1 signalling or glycolysis pathways restored M\u2010MDSC function and mitigated NEC severity. These findings complement our previous work on BCG's effects on polymorphonuclear (PMN)\u2010MDSCs and highlight the dual role of BCG: while it provides protective benefits in certain contexts, it may also increase NEC risk in preterm infants by disrupting MDSC\u2010mediated immune tolerance. This study offers critical insights into the mechanisms underlying BCG's off\u2010target effects and underscores the necessity of tailored vaccination strategies for preterm infants to minimise potential risks.<\/jats:p>","DOI":"10.1111\/imm.13946","type":"journal-article","created":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T20:45:56Z","timestamp":1747860356000},"page":"501-517","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["<scp>BCG<\/scp> Vaccination Reprograms the Function of M\u2010<scp>MDSCs<\/scp> and Aggravates Necrotizing Enterocolitis in Neonates"],"prefix":"10.1111","volume":"175","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1669-3003","authenticated-orcid":false,"given":"Yingying","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory, State Key Laboratory of Respiratory Disease, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Disease The First Affiliated Hospital of Guangzhou Medical University  Guangzhou China"},{"name":"Zhongshan School of Medicine, Sun Yat\u2010sen University  Guangzhou China"},{"name":"Tianjin Institute of Immunology, Key Laboratory of Immune Microenvironment and Disease of the Ministry of Education, Department of Immunology, School of Basic Medical Sciences Tianjin Medical University  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Li","sequence":"additional","affiliation":[{"name":"Tianjin Institute of Immunology, Key Laboratory of Immune Microenvironment and Disease of the Ministry of Education, Department of Immunology, School of Basic Medical Sciences Tianjin Medical University  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongmei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Tianjin Institute of Immunology, Key Laboratory of Immune Microenvironment and Disease of the Ministry of Education, Department of Immunology, School of Basic Medical Sciences Tianjin Medical University  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fajie","family":"Zhao","sequence":"additional","affiliation":[{"name":"Tianjin Institute of Immunology, Key Laboratory of Immune Microenvironment and Disease of the Ministry of Education, Department of Immunology, School of Basic Medical Sciences Tianjin Medical University  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5964-1599","authenticated-orcid":false,"given":"Jie","family":"Zhou","sequence":"additional","affiliation":[{"name":"Tianjin Institute of Immunology, Key Laboratory of Immune Microenvironment and Disease of the Ministry of Education, Department of Immunology, School of Basic Medical Sciences Tianjin Medical University  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,5,21]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1080\/21645515.2017.1334026"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.3310\/hta17370"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.3934\/microbiol.2021007"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.4161\/hv.7.1.13848"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaf1098"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2017.12.010"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1159\/000355628"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02806"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijgo.13195"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamapediatrics.2018.4038"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-020-00803-2"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.2223\/1307"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12887-015-0452-2"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1080\/21645515.2022.2080443"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1136\/adc.69.3_spec_no.309"},{"issue":"8","key":"e_1_2_9_17_1","first-page":"679","article-title":"Bacille Calmette Guerin Vaccination in Pre\u2010Term Infants","volume":"2","author":"Sedaghatian M. 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