{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T19:20:56Z","timestamp":1783711256826,"version":"3.55.0"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2020,1,28]],"date-time":"2020-01-28T00:00:00Z","timestamp":1580169600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["GNT1051228"],"award-info":[{"award-number":["GNT1051228"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["GNT1099680"],"award-info":[{"award-number":["GNT1099680"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001782","name":"University of Melbourne","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001782","id-type":"DOI","asserted-by":"publisher"}]},{"name":"European Society of Paediatric Infectious Diseases"},{"DOI":"10.13039\/100012697","name":"Clifford Craig Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012697","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Netherlands Organization for Scientific Research"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,6,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>BCG vaccination has beneficial nonspecific (heterologous) effects that protect against nonmycobacterial infections. We have previously reported that BCG vaccination at birth alters in vitro cytokine responses to heterologous stimulants in the neonatal period. This study investigated heterologous responses in 167 infants in the same trial 7 months after randomization.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A whole-blood assay was used to interrogate in vitro cytokine responses to heterologous stimulants (killed pathogens) and Toll-like receptor (TLR) ligands.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared to BCG-naive infants, BCG-vaccinated infants had increased production of interferon gamma (IFN-\u03b3) and monokine induced by gamma interferon (MIG) (CXCL9) in response to mycobacterial stimulation and decreased production of IFN-\u03b3 in response to heterologous stimulation and TLR ligands. Reduced IFN-\u03b3 responses were attributable to a decrease in the proportion of infants who mounted a detectable IFN-\u03b3 response. BCG-vaccinated infants also had increased production of MIG (CXCL9) and interleukin-8 (IL-8), and decreased production of IL-10, macrophage inflammatory protein-1\u03b1 (MIP-1\u03b1), and MIP-1\u03b2, the pattern of which varied by stimulant. IL-1Ra responses following TLR1\/2 (Pam3CYSK4) stimulation were increased in BCG-vaccinated infants. Both sex and maternal BCG vaccination status influenced the effect of neonatal BCG vaccination.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>BCG vaccination leads to changes in IFN-\u03b3 responsiveness to heterologous stimulation. BCG-induced changes in other cytokine responses to heterologous stimulation vary by pathogen.<\/jats:p><\/jats:sec>","DOI":"10.1093\/infdis\/jiaa030","type":"journal-article","created":{"date-parts":[[2020,1,27]],"date-time":"2020-01-27T20:10:18Z","timestamp":1580155818000},"page":"1999-2009","source":"Crossref","is-referenced-by-count":30,"title":["Neonatal BCG Vaccination Reduces Interferon-\u03b3 Responsiveness to Heterologous Pathogens in Infants From a Randomized Controlled Trial"],"prefix":"10.1093","volume":"221","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9542-1582","authenticated-orcid":false,"given":"Bridget","family":"Freyne","sequence":"first","affiliation":[{"name":"Infectious Diseases and Microbiology Group, Murdoch Children\u2019s Research Institute, Royal Children\u2019s Hospital Melbourne, Parkville, Australia"},{"name":"Department of Paediatrics, The University of Melbourne, Parkville, Australia"},{"name":"Institute of Infection and Global Health, The 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M","family":"Robins-Browne","sequence":"first","affiliation":[{"name":"Infectious Diseases and Microbiology Group, Murdoch Children\u2019s Research Institute, Royal Children\u2019s Hospital Melbourne, Parkville, Australia"},{"name":"Department of Microbiology and Immunology, The University of Melbourne, Parkville, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihai G","family":"Netea","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Radboud Institute for Molecular Life Sciences, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands"},{"name":"Radboud Center for Infectious Diseases, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katie L","family":"Flanagan","sequence":"first","affiliation":[{"name":"University of Tasmania, Launceston, Australia"},{"name":"Monash University, Clayton, 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