{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T20:07:06Z","timestamp":1772136426248,"version":"3.50.1"},"reference-count":88,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,5,25]],"date-time":"2025-05-25T00:00:00Z","timestamp":1748131200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,5,25]],"date-time":"2025-05-25T00:00:00Z","timestamp":1748131200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/100001655","name":"Grayson-Jockey Club Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001655","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020968","name":"Boehringer-Ingelheim Animal Health","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100020968","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Texas A&M University Link Equine Research Endowment"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-025-02060-5","type":"journal-article","created":{"date-parts":[[2025,5,25]],"date-time":"2025-05-25T01:32:59Z","timestamp":1748136779000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Enteral immunization with live bacteria reprograms innate immune cells and protects neonatal foals from pneumonia"],"prefix":"10.1038","volume":"15","author":[{"given":"Bibiana Petri","family":"da Silveira","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susanne K.","family":"Kahn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca M.","family":"Legere","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jocelyne M.","family":"Bray","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hannah M.","family":"Cole-Pfeiffer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael C.","family":"Golding","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noah D.","family":"Cohen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela I.","family":"Bordin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,5,25]]},"reference":[{"key":"2060_CR1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.coi.2016.04.004","volume":"41","author":"E Mohr","year":"2016","unstructured":"Mohr, E. & Siegrist, C. A. Vaccination in early life: Standing up to the challenges. Curr. Opin. Immunol. 41, 1\u20138. https:\/\/doi.org\/10.1016\/j.coi.2016.04.004 (2016).","journal-title":"Curr. Opin. Immunol."},{"key":"2060_CR2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1476-8518-5-1","volume":"5","author":"MJ Flaminio","year":"2007","unstructured":"Flaminio, M. J. et al. The effect of CpG-ODN on antigen presenting cells of the foal. J. Immune Based Ther. Vaccines  5, 1. https:\/\/doi.org\/10.1186\/1476-8518-5-1 (2007).","journal-title":"J. Immune Based Ther. Vaccines"},{"key":"2060_CR3","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1128\/CVI.00336-08","volume":"16","author":"MJ Flaminio","year":"2009","unstructured":"Flaminio, M. J., Nydam, D. V., Marquis, H., Matychak, M. B. & Giguere, S. Foal monocyte-derived dendritic cells become activated upon Rhodococcus equi infection. Clin. Vaccine Immunol.: CVI. 16, 176\u2013183. https:\/\/doi.org\/10.1128\/CVI.00336-08 (2009).","journal-title":"Clin. Vaccine Immunol.: CVI"},{"key":"2060_CR4","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1016\/j.vetimm.2009.02.007","volume":"130","author":"IS Pargass","year":"2009","unstructured":"Pargass, I. S. et al. The influence of age and Rhodococcus equi infection on CD1 expression by equine antigen presenting cells. Vet. Immunol. Immunopathol. 130, 197\u2013209. https:\/\/doi.org\/10.1016\/j.vetimm.2009.02.007 (2009).","journal-title":"Vet. Immunol. Immunopathol."},{"key":"2060_CR5","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.vetimm.2018.11.020","volume":"210","author":"BS Lopez","year":"2019","unstructured":"Lopez, B. S. et al. The effect of age on foal monocyte-derived dendritic cell (MoDC) maturation and function after exposure to killed bacteria. Vet. Immunol. Immunopathol. 210, 38\u201345. https:\/\/doi.org\/10.1016\/j.vetimm.2018.11.020 (2019).","journal-title":"Vet. Immunol. Immunopathol."},{"key":"2060_CR6","doi-asserted-by":"publisher","first-page":"e10407","DOI":"10.1371\/journal.pone.0010407","volume":"5","author":"M Nguyen","year":"2010","unstructured":"Nguyen, M. et al. Acquisition of adult-like TLR4 and TLR9 responses during the first year of life. PLoS ONE. 5, e10407. https:\/\/doi.org\/10.1371\/journal.pone.0010407 (2010).","journal-title":"PLoS ONE"},{"key":"2060_CR7","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1038\/ni.3123","volume":"16","author":"A Iwasaki","year":"2015","unstructured":"Iwasaki, A. & Medzhitov, R. Control of adaptive immunity by the innate immune system. Nat. Immunol. 16, 343\u2013353. https:\/\/doi.org\/10.1038\/ni.3123 (2015).","journal-title":"Nat. Immunol."},{"key":"2060_CR8","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1007\/s00281-017-0654-9","volume":"39","author":"A Saso","year":"2017","unstructured":"Saso, A. & Kampmann, B. Vaccine responses in newborns. Semin Immunopathol. 39, 627\u2013642. https:\/\/doi.org\/10.1007\/s00281-017-0654-9 (2017).","journal-title":"Semin Immunopathol."},{"key":"2060_CR9","doi-asserted-by":"publisher","first-page":"168718","DOI":"10.1016\/j.jmb.2024.168718","volume":"436","author":"V Verhasselt","year":"2024","unstructured":"Verhasselt, V., Marchant, A. & Kollmann, T. R. Per Os to orotection\u2014targeting the oral route to enhance immune-mediated protection from disease of the human newborn. J. Mol. Biol. 436, 168718. https:\/\/doi.org\/10.1016\/j.jmb.2024.168718 (2024).","journal-title":"J. Mol. Biol."},{"key":"2060_CR10","doi-asserted-by":"publisher","unstructured":"Cirovic, B. et al. BCG vaccination in humans elicits trained immunity via the hematopoietic progenitor compartment. Cell Host Microbe 28, 322\u2013334 e325, (2020). https:\/\/doi.org\/10.1016\/j.chom.2020.05.014","DOI":"10.1016\/j.chom.2020.05.014"},{"key":"2060_CR11","doi-asserted-by":"publisher","first-page":"13","DOI":"10.3389\/fpubh.2018.00013","volume":"6","author":"A Andersen","year":"2018","unstructured":"Andersen, A. et al. National immunization campaigns with oral polio vaccine reduce all-cause mortality: A natural experiment within seven randomized trials. Front. Public. Health. 6, 13. https:\/\/doi.org\/10.3389\/fpubh.2018.00013 (2018).","journal-title":"Front. Public. Health"},{"key":"2060_CR12","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1159\/000356035","volume":"105","author":"O Levy","year":"2014","unstructured":"Levy, O. & Wynn, J. L. A prime time for trained immunity: Innate immune memory in newborns and infants. Neonatology 105, 136\u2013141. https:\/\/doi.org\/10.1159\/000356035 (2014).","journal-title":"Neonatology"},{"key":"2060_CR13","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1016\/j.cveq.2014.08.010","volume":"30","author":"ND Cohen","year":"2014","unstructured":"Cohen, N. D. Rhodococcus equi foal pneumonia. Vet. Clin. North. Am. Equine Pract. 30, 609\u2013622. https:\/\/doi.org\/10.1016\/j.cveq.2014.08.010 (2014).","journal-title":"Vet. Clin. North. Am. Equine Pract."},{"key":"2060_CR14","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1016\/j.cmi.2018.04.033","volume":"25","author":"WV Lin","year":"2019","unstructured":"Lin, W. V., Kruse, R. L., Yang, K. & Musher, D. M. Diagnosis and management of pulmonary infection due to Rhodococcus equi. Clin. Microbiol. Infect. 25, 310\u2013315. https:\/\/doi.org\/10.1016\/j.cmi.2018.04.033 (2019).","journal-title":"Clin. Microbiol. Infect."},{"key":"2060_CR15","doi-asserted-by":"publisher","first-page":"3548","DOI":"10.1128\/IAI.67.7.3548-3557.1999","volume":"67","author":"S Gigu\u00e8re","year":"1999","unstructured":"Gigu\u00e8re, S. et al. Role of the 85-kilobase plasmid and plasmid-encoded virulence-associated protein A in intracellular survival and virulence of Rhodococcus equi. Infect. Immun. 67, 3548\u20133557. https:\/\/doi.org\/10.1128\/IAI.67.7.3548-3557.1999 (1999).","journal-title":"Infect. Immun."},{"key":"2060_CR16","doi-asserted-by":"publisher","unstructured":"Horowitz, M. L. et al. Application of Sartwell\u2019s model (lognormal distribution of incubation periods) to age at onset and age at death of foals with Rhodococcus equi pneumonia as evidence of perinatal infection. J. Vet. Intern. Med. 15, 171\u2013175. https:\/\/doi.org\/10.1892\/0891-6640(2001)015%3C0171:aosmld%3E2.3.co;2 (2001).","DOI":"10.1892\/0891-6640(2001)015%3C0171:aosmld%3E2.3.co;2"},{"key":"2060_CR17","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1016\/j.vetmic.2013.09.018","volume":"167","author":"M Sanz","year":"2013","unstructured":"Sanz, M. et al. The effect of bacterial dose and foal age at challenge on Rhodococcus equi infection. Vet. Microbiol. 167, 623\u2013631. https:\/\/doi.org\/10.1016\/j.vetmic.2013.09.018 (2013).","journal-title":"Vet. Microbiol."},{"key":"2060_CR18","doi-asserted-by":"publisher","first-page":"674","DOI":"10.1016\/j.vaccine.2008.11.040","volume":"27","author":"T Liu","year":"2009","unstructured":"Liu, T., Nerren, J., Liu, M., Martens, R. & Cohen, N. Basal and stimulus-induced cytokine expression is selectively impaired in peripheral blood mononuclear cells of newborn foals. Vaccine 27, 674\u2013683. https:\/\/doi.org\/10.1016\/j.vaccine.2008.11.040 (2009).","journal-title":"Vaccine"},{"key":"2060_CR19","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1016\/s0165-2427(00)00149-5","volume":"73","author":"MJ Flaminio","year":"2000","unstructured":"Flaminio, M. J. et al. Characterization of peripheral blood and pulmonary leukocyte function in healthy foals. Vet. Immunol. Immunopathol. 73, 267\u2013285. https:\/\/doi.org\/10.1016\/s0165-2427(00)00149-5 (2000).","journal-title":"Vet. Immunol. Immunopathol."},{"key":"2060_CR20","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/s0165-2427(03)00021-7","volume":"92","author":"NK Boyd","year":"2003","unstructured":"Boyd, N. K. et al. Temporal changes in cytokine expression of foals during the first month of life. Vet. Immunol. Immunopathol. 92, 75\u201385. https:\/\/doi.org\/10.1016\/s0165-2427(03)00021-7 (2003).","journal-title":"Vet. Immunol. Immunopathol."},{"key":"2060_CR21","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1016\/j.vetimm.2006.02.010","volume":"112","author":"CC Breathnach","year":"2006","unstructured":"Breathnach, C. C. et al. Foals are interferon gamma-deficient at birth. Vet. Immunol. Immunopathol. 112, 199\u2013209. https:\/\/doi.org\/10.1016\/j.vetimm.2006.02.010 (2006).","journal-title":"Vet. Immunol. Immunopathol."},{"key":"2060_CR22","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1016\/j.dci.2018.06.012","volume":"87","author":"SV Dindot","year":"2018","unstructured":"Dindot, S. V. et al. Postnatal changes in epigenetic modifications of neutrophils of foals are associated with increased ROS function and regulation of neutrophil function. Dev. Comp. Immunol. 87, 182\u2013187. https:\/\/doi.org\/10.1016\/j.dci.2018.06.012 (2018).","journal-title":"Dev. Comp. Immunol."},{"key":"2060_CR23","doi-asserted-by":"publisher","DOI":"10.1111\/evj.14214","author":"BP da Silveira","year":"2024","unstructured":"da Silveira, B. P., Cohen, N. D., Lawhon, S. D., Watson, R. O. & Bordin A. I. Protective immune response against Rhodococcus equi: An innate immunity-focused review. Equine Vet. J. https:\/\/doi.org\/10.1111\/evj.14214 (2024).","journal-title":"Equine Vet. J."},{"key":"2060_CR24","doi-asserted-by":"publisher","first-page":"e109865","DOI":"10.1371\/journal.pone.0109865","volume":"9","author":"ND Cohen","year":"2014","unstructured":"Cohen, N. D. et al. Intramuscular administration of a synthetic CpG-oligodeoxynucleotide modulates functional responses of neutrophils of neonatal foals. PLoS One  9, e109865. https:\/\/doi.org\/10.1371\/journal.pone.0109865 (2014).","journal-title":"PLoS One"},{"key":"2060_CR25","doi-asserted-by":"publisher","first-page":"7040","DOI":"10.1128\/IAI.73.10.7040-7042.2005","volume":"73","author":"RJ Martens","year":"2005","unstructured":"Martens, R. J., Cohen, N. D., Jones, S. L., Moore, T. A. & Edwards, J. F. Protective role of neutrophils in mice experimentally infected with Rhodococcus equi. Infect. Immun. 73, 7040\u20137042. https:\/\/doi.org\/10.1128\/IAI.73.10.7040-7042.2005 (2005).","journal-title":"Infect. Immun."},{"key":"2060_CR26","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/j.vetimm.2004.02.010","volume":"100","author":"MK Chaffin","year":"2004","unstructured":"Chaffin, M. K. et al. Hematologic and immunophenotypic factors associated with development of Rhodococcus equi pneumonia of foals at equine breeding farms with endemic infection. Vet. Immunol. Immunopathol. 100, 33\u201348. https:\/\/doi.org\/10.1016\/j.vetimm.2004.02.010 (2004).","journal-title":"Vet. Immunol. Immunopathol."},{"key":"2060_CR27","doi-asserted-by":"publisher","first-page":"356","DOI":"10.2460\/ajvr.1997.58.04.356","volume":"58","author":"JF Prescott","year":"1997","unstructured":"Prescott, J. F. et al. Use of Rhodococcus equi virulence-associated protein for immunization of foals against R. equi pneumonia. Am. J. Vet. Res. 58, 356\u2013359 (1997).","journal-title":"Am. J. Vet. Res."},{"key":"2060_CR28","first-page":"161","volume":"77","author":"KL Lohmann","year":"2013","unstructured":"Lohmann, K. L. et al. Failure of a VapA\/CpG oligodeoxynucleotide vaccine to protect foals against experimental Rhocococcus equi pneumonia despite induction of VapA-specific antibody and interferon-gamma response. Can. J. Vet. Res. 77, 161\u2013169 (2013).","journal-title":"Can. J. Vet. Res."},{"key":"2060_CR29","doi-asserted-by":"publisher","first-page":"e0148111","DOI":"10.1371\/journal.pone.0148111","volume":"11","author":"JN Rocha","year":"2016","unstructured":"Rocha, J. N. et al. Oral administration of electron-beam inactivated Rhodococcus equi failed to protect foals against intrabronchial infection with live, virulent R. equi. PLoS One. 11, e0148111. https:\/\/doi.org\/10.1371\/journal.pone.0148111 (2016).","journal-title":"PLoS One"},{"key":"2060_CR30","first-page":"356","volume":"43","author":"JF Prescott","year":"1979","unstructured":"Prescott, J. F., Markham, R. J. & Johnson, J. A. Cellular and humoral immune response of foals to vaccination with Corynebacterium equi. Can. J. Comp. Med. 43, 356\u2013364 (1979).","journal-title":"Can. J. Comp. Med."},{"key":"2060_CR31","doi-asserted-by":"publisher","first-page":"998","DOI":"10.1016\/j.vaccine.2007.10.069","volume":"26","author":"AM Lopez","year":"2008","unstructured":"Lopez, A. M., Townsend, H. G., Allen, A. L. & Hondalus, M. K. Safety and immunogenicity of a live-attenuated auxotrophic candidate vaccine against the intracellular pathogen Rhodococcus equi. Vaccine 26, 998\u20131009. https:\/\/doi.org\/10.1016\/j.vaccine.2007.10.069 (2008). doi:S0264-410X(07)01263-7 [pii].","journal-title":"Vaccine"},{"key":"2060_CR32","first-page":"444","volume":"51","author":"JM Chirino-Trejo","year":"1987","unstructured":"Chirino-Trejo, J. M., Prescott, J. F. & Yager, J. A. Protection of foals against experimental Rhodococcus equi pneumonia by oral immunization. Can. J. Vet. Res. 51, 444\u2013447 (1987).","journal-title":"Can. J. Vet. Res."},{"key":"2060_CR33","doi-asserted-by":"publisher","first-page":"5760","DOI":"10.1016\/j.vaccine.2005.07.050","volume":"23","author":"KE Hooper-McGrevy","year":"2005","unstructured":"Hooper-McGrevy, K. E., Wilkie, B. N. & Prescott, J. F. Virulence-associated protein-specific serum Immunoglobulin G-isotype expression in young foals protected against Rhodococcus equi pneumonia by oral immunization with virulent R. equi. Vaccine 23, 5760\u20135767. https:\/\/doi.org\/10.1016\/j.vaccine.2005.07.050 (2005).","journal-title":"Vaccine"},{"key":"2060_CR34","doi-asserted-by":"publisher","first-page":"e1002181","DOI":"10.1371\/journal.ppat.1002181","volume":"7","author":"R van der Geize","year":"2011","unstructured":"van der Geize, R., Grommen, A. W., Hessels, G. I., Jacobs, A. A. & Dijkhuizen, L. The steroid catabolic pathway of the intracellular pathogen Rhodococcus equi is important for pathogenesis and a target for vaccine development. PLoS Pathog. 7, e1002181. https:\/\/doi.org\/10.1371\/journal.ppat.1002181 (2011).","journal-title":"PLoS Pathog"},{"key":"2060_CR35","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1097\/SHK.0b013e3182184ee7","volume":"36","author":"LW Chen","year":"2011","unstructured":"Chen, L. W., Chen, P. H. & Hsu, C. M. Commensal microflora contribute to host defense against Escherichia coli pneumonia through Toll-like receptors. Shock 36, 67\u201375. https:\/\/doi.org\/10.1097\/SHK.0b013e3182184ee7 (2011).","journal-title":"Shock"},{"key":"2060_CR36","doi-asserted-by":"publisher","first-page":"1411","DOI":"10.4049\/jimmunol.1101682","volume":"188","author":"CT Fagundes","year":"2012","unstructured":"Fagundes, C. T. et al. Transient TLR activation restores inflammatory response and ability to control pulmonary bacterial infection in germfree mice. J. Immunol. 188, 1411\u20131420. https:\/\/doi.org\/10.4049\/jimmunol.1101682 (2012).","journal-title":"J. Immunol."},{"key":"2060_CR37","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1136\/gutjnl-2015-309728","volume":"65","author":"TJ Schuijt","year":"2016","unstructured":"Schuijt, T. J. et al. The gut microbiota plays a protective role in the host defence against Pneumococcal pneumonia. Gut 65, 575\u2013583. https:\/\/doi.org\/10.1136\/gutjnl-2015-309728 (2016).","journal-title":"Gut"},{"key":"2060_CR38","first-page":"280","volume":"44","author":"JF Prescott","year":"1980","unstructured":"Prescott, J. F., Johnson, J. A. & Markham, R. J. Experimental studies on the pathogenesis of Corynebacterium equi infection in foals. Can. J. Comp. Med. 44, 280\u2013288 (1980).","journal-title":"Can. J. Comp. Med."},{"key":"2060_CR39","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1016\/0378-1135(87)90119-2","volume":"14","author":"S Takai","year":"1987","unstructured":"Takai, S., Kawazu, S. & Tsubaki, S. Humoral immune response of foals to experimental infection with Rhodococcus equi. Vet. Microbiol. 14, 321\u2013327. https:\/\/doi.org\/10.1016\/0378-1135(87)90119-2 (1987).","journal-title":"Vet. Microbiol."},{"key":"2060_CR40","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1016\/j.vetimm.2011.03.015","volume":"141","author":"SP Harris","year":"2011","unstructured":"Harris, S. P., Hines, M. T., Mealey, R. H., Alperin, D. C. & Hines, S. A. Early development of cytotoxic T lymphocytes in neonatal foals following oral inoculation with Rhodococcus equi. Vet. Immunol. Immunopathol. 141, 312\u2013316. https:\/\/doi.org\/10.1016\/j.vetimm.2011.03.015 (2011).","journal-title":"Vet. Immunol. Immunopathol."},{"key":"2060_CR41","doi-asserted-by":"publisher","first-page":"e105367","DOI":"10.1371\/journal.pone.0105367","volume":"9","author":"AI Bordin","year":"2014","unstructured":"Bordin, A. I. et al. Immunogenicity of an electron beam inactivated Rhodococcus equi vaccine in neonatal foals. PLoS One . 9, e105367. https:\/\/doi.org\/10.1371\/journal.pone.0105367 (2014).","journal-title":"PLoS One"},{"key":"2060_CR42","doi-asserted-by":"publisher","unstructured":"McGill, M. P. & Threadgill, D. W. Adding robustness to rigor and reproducibility for the three Rs of improving translational medical research. J. Clin. Invest. 133 https:\/\/doi.org\/10.1172\/JCI173750 (2023).","DOI":"10.1172\/JCI173750"},{"key":"2060_CR43","doi-asserted-by":"publisher","first-page":"107596","DOI":"10.1016\/j.isci.2023.107596","volume":"26","author":"BN Kain","year":"2023","unstructured":"Kain, B. N. et al. Hematopoietic stem and progenitor cells confer cross-protective trained immunity in mouse models. iScience 26, 107596. https:\/\/doi.org\/10.1016\/j.isci.2023.107596 (2023).","journal-title":"iScience"},{"key":"2060_CR44","doi-asserted-by":"publisher","first-page":"4928","DOI":"10.4049\/jimmunol.162.8.4928","volume":"162","author":"S Gasperini","year":"1999","unstructured":"Gasperini, S. et al. Gene expression and production of the monokine induced by IFN-gamma (MIG), IFN-inducible T cell alpha chemoattractant (I-TAC), and IFN-gamma-inducible protein-10 (IP-10) chemokines by human neutrophils. J. Immunol. 162, 4928\u20134937 (1999).","journal-title":"J. Immunol."},{"key":"2060_CR45","doi-asserted-by":"publisher","first-page":"e0185956","DOI":"10.1371\/journal.pone.0185956","volume":"12","author":"MA Ellison","year":"2017","unstructured":"Ellison, M. A., Gearheart, C. M., Porter, C. C. & Ambruso, D. R. IFN-gamma alters the expression of diverse immunity related genes in a cell culture model designed to represent maturing neutrophils. PLoS One 12, e0185956. https:\/\/doi.org\/10.1371\/journal.pone.0185956 (2017).","journal-title":"PLoS One"},{"key":"2060_CR46","doi-asserted-by":"publisher","unstructured":"Ambruso, D. R. et al. In vivo interferon-gamma induced changes in gene expression dramatically alter neutrophil phenotype. PLoS One 17, e0263370, (2022). https:\/\/doi.org\/10.1371\/journal.pone.0263370","DOI":"10.1371\/journal.pone.0263370"},{"key":"2060_CR47","doi-asserted-by":"publisher","first-page":"17537","DOI":"10.1073\/pnas.1202870109","volume":"109","author":"J Kleinnijenhuis","year":"2012","unstructured":"Kleinnijenhuis, J. et al. Bacille Calmette-Guerin induces NOD2-dependent nonspecific protection from reinfection via epigenetic reprogramming of monocytes. Proc. Natl. Acad. Sci. U S A 109, 17537\u201317542. https:\/\/doi.org\/10.1073\/pnas.1202870109 (2012).","journal-title":"Proc. Natl. Acad. Sci. U S A"},{"key":"2060_CR48","doi-asserted-by":"publisher","unstructured":"Arts, R. J. W. et al. BCG vaccination protects against experimental viral infection in humans through the induction of cytokines associated with trained immunity. Cell Host Microbe 23, 89\u2013100 e105, (2018). https:\/\/doi.org\/10.1016\/j.chom.2017.12.010","DOI":"10.1016\/j.chom.2017.12.010"},{"key":"2060_CR49","doi-asserted-by":"publisher","unstructured":"De Gobbi, M. et al. Generation of bivalent chromatin domains during cell fate decisions. Epigenet. Chromatin 4. https:\/\/doi.org\/10.1186\/1756-8935-4-9 (2011).","DOI":"10.1186\/1756-8935-4-9"},{"key":"2060_CR50","doi-asserted-by":"publisher","first-page":"295","DOI":"10.2460\/ajvr.1988.49.03.295","volume":"49","author":"JG Martens","year":"1988","unstructured":"Martens, J. G., Martens, R. J. & Renshaw, H. W. Rhodococcus (Corynebacterium) equi: Bactericidal capacity of neutrophils from neonatal and adult horses. Am. J. Vet. Res. 49, 295\u2013299 (1988).","journal-title":"Am. J. Vet. Res."},{"key":"2060_CR51","doi-asserted-by":"publisher","first-page":"4167","DOI":"10.1128\/iai.62.10.4167-4175.1994","volume":"62","author":"MK Hondalus","year":"1994","unstructured":"Hondalus, M. K. & Mosser, D. M. Survival and replication of Rhodococcus equi in macrophages. Infect. Immun. 62, 4167\u20134175 (1994).","journal-title":"Infect. Immun."},{"key":"2060_CR52","doi-asserted-by":"publisher","first-page":"2483","DOI":"10.1038\/s41598-021-82049-y","volume":"11","author":"AI Bordin","year":"2021","unstructured":"Bordin, A. I. et al. Host-directed therapy in foals can enhance functional innate immunity and reduce severity of Rhodococcus equi pneumonia. Sci. Rep. 11, 2483. https:\/\/doi.org\/10.1038\/s41598-021-82049-y (2021).","journal-title":"Sci. Rep."},{"key":"2060_CR53","doi-asserted-by":"publisher","first-page":"356","DOI":"10.1038\/ni.3375","volume":"17","author":"A Rivera","year":"2016","unstructured":"Rivera, A., Siracusa, M. C., Yap, G. S. & Gause, W. C. Innate cell communication kick-starts pathogen-specific immunity. Nat. Immunol. 17, 356\u2013363. https:\/\/doi.org\/10.1038\/ni.3375 (2016).","journal-title":"Nat. Immunol."},{"key":"2060_CR54","doi-asserted-by":"publisher","unstructured":"Yao, Y. et al. Induction of autonomous memory alveolar macrophages requires T cell help and is critical to trained immunity. Cell 175, 1634\u20131650 e1617. https:\/\/doi.org\/10.1016\/j.cell.2018.09.042 (2018).","DOI":"10.1016\/j.cell.2018.09.042"},{"key":"2060_CR55","doi-asserted-by":"publisher","first-page":"706583","DOI":"10.3389\/fimmu.2021.706583","volume":"12","author":"DM Murphy","year":"2021","unstructured":"Murphy, D. M., Mills, K. H. G. & Basdeo, S. A. The effects of trained innate immunity on T cell responses; clinical implications and knowledge gaps for future research. Front. Immunol. 12, 706583. https:\/\/doi.org\/10.3389\/fimmu.2021.706583 (2021).","journal-title":"Front. Immunol."},{"key":"2060_CR56","doi-asserted-by":"publisher","first-page":"1687","DOI":"10.1038\/s41590-022-01354-4","volume":"23","author":"M Jeyanathan","year":"2022","unstructured":"Jeyanathan, M. et al. Parenteral BCG vaccine induces lung-resident memory macrophages and trained immunity via the gut-lung axis. Nat. Immunol. 23, 1687\u20131702. https:\/\/doi.org\/10.1038\/s41590-022-01354-4 (2022).","journal-title":"Nat. Immunol."},{"key":"2060_CR57","doi-asserted-by":"publisher","first-page":"105088","DOI":"10.1016\/j.micpath.2021.105088","volume":"158","author":"MVT Silva","year":"2021","unstructured":"Silva, M. V. T. et al. The role of IL-32 in Bacillus Calmette-Guerin (BCG)-induced trained immunity in infections caused by different Leishmania spp. Microb. Pathog. 158, 105088. https:\/\/doi.org\/10.1016\/j.micpath.2021.105088 (2021).","journal-title":"Microb. Pathog"},{"key":"2060_CR58","doi-asserted-by":"publisher","unstructured":"Dos Santos, J. C. et al. Beta-glucan-induced trained immunity protects against Leishmania braziliensis infection: A crucial role for IL-32. Cell Rep. 28, 2659\u20132672 e2656. https:\/\/doi.org\/10.1016\/j.celrep.2019.08.004  (2019).","DOI":"10.1016\/j.celrep.2019.08.004"},{"key":"2060_CR59","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1038\/s41588-018-0298-2","volume":"51","author":"S Fanucchi","year":"2019","unstructured":"Fanucchi, S. et al. Immune genes are primed for robust transcription by proximal long noncoding RNAs located in nuclear compartments. Nat. Genet. 51, 138\u2013150. https:\/\/doi.org\/10.1038\/s41588-018-0298-2 (2019).","journal-title":"Nat. Genet."},{"key":"2060_CR60","doi-asserted-by":"publisher","first-page":"155773","DOI":"10.1016\/j.cyto.2021.155773","volume":"150","author":"LU Teufel","year":"2022","unstructured":"Teufel, L. U., Arts, R. J. W., Netea, M. G., Dinarello, C. A. & Joosten, L. A. B. IL-1 family cytokines as drivers and inhibitors of trained immunity. Cytokine 150, 155773. https:\/\/doi.org\/10.1016\/j.cyto.2021.155773 (2022).","journal-title":"Cytokine"},{"key":"2060_CR61","doi-asserted-by":"publisher","unstructured":"Rocha, J. N. et al. PNAG-specific equine IgG1 mediates significantly greater opsonization and killing of Prescottella equi (formerly Rhodococcus equi) than does IgG4\/7. Vaccine 37, 1142\u20131150, (2019). https:\/\/doi.org\/10.1016\/j.vaccine.2019.01.028.","DOI":"10.1016\/j.vaccine.2019.01.028"},{"key":"2060_CR62","doi-asserted-by":"publisher","first-page":"965305","DOI":"10.3389\/fimmu.2022.965305","volume":"13","author":"A Trzeciak","year":"2022","unstructured":"Trzeciak, A. et al. Neutrophil heterogeneity in complement C1q expression associated with sepsis mortality. Front. Immunol. 13, 965305. https:\/\/doi.org\/10.3389\/fimmu.2022.965305 (2022).","journal-title":"Front. Immunol."},{"key":"2060_CR63","doi-asserted-by":"publisher","first-page":"e73610","DOI":"10.1371\/journal.pone.0073610","volume":"8","author":"D Howie","year":"2013","unstructured":"Howie, D., Garcia Rueda, H., Brown, M. H. & Waldmann, H. Secreted and transmembrane 1A is a novel co-stimulatory ligand. PLoS One  8, e73610. https:\/\/doi.org\/10.1371\/journal.pone.0073610 (2013).","journal-title":"PLoS One"},{"key":"2060_CR64","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1189\/jlb.1011498","volume":"91","author":"T Wang","year":"2012","unstructured":"Wang, T. et al. K12\/SECTM1, an interferon-gamma regulated molecule, synergizes with CD28 to costimulate human T cell proliferation. J. Leukoc. Biol. 91, 449\u2013459. https:\/\/doi.org\/10.1189\/jlb.1011498 (2012).","journal-title":"J. Leukoc. Biol."},{"key":"2060_CR65","doi-asserted-by":"publisher","first-page":"1108","DOI":"10.1038\/jid.2013.437","volume":"134","author":"T Wang","year":"2014","unstructured":"Wang, T. et al. SECTM1 produced by tumor cells attracts human monocytes via CD7-mediated activation of the PI3K pathway. J. Invest. Dermatol. 134, 1108\u20131118. https:\/\/doi.org\/10.1038\/jid.2013.437 (2014).","journal-title":"J. Invest. Dermatol."},{"key":"2060_CR66","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1159\/000455969","volume":"9","author":"K Subramanian","year":"2017","unstructured":"Subramanian, K., Bergman, P. & Henriques-Normark, B. Vitamin D promotes Pneumococcal killing and modulates inflammatory responses in primary human neutrophils. J. Innate Immun. 9, 375\u2013386. https:\/\/doi.org\/10.1159\/000455969 (2017).","journal-title":"J. Innate Immun."},{"key":"2060_CR67","doi-asserted-by":"publisher","unstructured":"Hirsch, D., Archer, F. E., Joshi-Kale, M., Vetrano, A. M. & Weinberger, B. Decreased anti-inflammatory responses to vitamin D in neonatal neutrophils. Mediators Inflamm. 598345, (2011). https:\/\/doi.org\/10.1155\/2011\/598345 (2011).","DOI":"10.1155\/2011\/598345"},{"key":"2060_CR68","doi-asserted-by":"publisher","first-page":"110593","DOI":"10.1016\/j.vetimm.2023.110593","volume":"259","author":"LJ Berghaus","year":"2023","unstructured":"Berghaus, L. J., Cathcart, J., Berghaus, R. D. & Hart, K. A. Age-related changes in vitamin D metabolism and vitamin D receptor expression in equine alveolar macrophages: A preliminary study. Vet. Immunol. Immunopathol. 259, 110593. https:\/\/doi.org\/10.1016\/j.vetimm.2023.110593 (2023).","journal-title":"Vet. Immunol. Immunopathol."},{"key":"2060_CR69","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1186\/s13148-016-0265-7","volume":"8","author":"JR Bermick","year":"2016","unstructured":"Bermick, J. R. et al. Neonatal monocytes exhibit a unique histone modification landscape. Clin. Epigenetics  8, 99. https:\/\/doi.org\/10.1186\/s13148-016-0265-7 (2016).","journal-title":"Clin. Epigenetics"},{"key":"2060_CR70","doi-asserted-by":"publisher","first-page":"1318","DOI":"10.1101\/gad.219626.113","volume":"27","author":"P Voigt","year":"2013","unstructured":"Voigt, P., Tee, W. W. & Reinberg, D. A double take on bivalent promoters. Genes Dev. 27, 1318\u20131338. https:\/\/doi.org\/10.1101\/gad.219626.113 (2013).","journal-title":"Genes Dev."},{"key":"2060_CR71","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1016\/j.stem.2008.11.011","volume":"4","author":"K Cui","year":"2009","unstructured":"Cui, K. et al. Chromatin signatures in multipotent human hematopoietic stem cells indicate the fate of bivalent genes during differentiation. Cell. Stem Cell. 4, 80\u201393. https:\/\/doi.org\/10.1016\/j.stem.2008.11.011 (2009).","journal-title":"Cell. Stem Cell."},{"key":"2060_CR72","doi-asserted-by":"publisher","unstructured":"Gray, J. et al. Intestinal commensal bacteria mediate lung mucosal immunity and promote resistance of newborn mice to infection. Sci. Transl Med. 9 https:\/\/doi.org\/10.1126\/scitranslmed.aaf9412 (2017).","DOI":"10.1126\/scitranslmed.aaf9412"},{"key":"2060_CR73","doi-asserted-by":"publisher","first-page":"63","DOI":"10.2460\/ajvr.68.1.63","volume":"68","author":"MB Grimm","year":"2007","unstructured":"Grimm, M. B. et al. Evaluation of fecal samples from mares as a source of Rhodococcus equi for their foals by use of quantitative bacteriologic culture and colony Immunoblot analyses. Am. J. Vet. Res. 68, 63\u201371. https:\/\/doi.org\/10.2460\/ajvr.68.1.63 (2007).","journal-title":"Am. J. Vet. Res."},{"key":"2060_CR74","doi-asserted-by":"publisher","first-page":"e1007160","DOI":"10.1371\/journal.ppat.1007160","volume":"14","author":"C Cywes-Bentley","year":"2018","unstructured":"Cywes-Bentley, C. et al. Antibody to poly-N-acetyl glucosamine provides protection against intracellular pathogens: Mechanism of action and validation in horse foals challenged with Rhodococcus equi. PLoS Pathog.  14, e1007160. https:\/\/doi.org\/10.1371\/journal.ppat.1007160 (2018).","journal-title":"PLoS Pathog."},{"key":"2060_CR75","doi-asserted-by":"publisher","first-page":"1139","DOI":"10.1111\/jvim.16409","volume":"36","author":"ND Cohen","year":"2022","unstructured":"Cohen, N. D. et al. Association of pneumonia with concentrations of virulent Rhodococcus equi in fecal swabs of foals before and after intrabronchial infection with virulent R. equi. J. Vet. Intern. Med. 36, 1139\u20131145. https:\/\/doi.org\/10.1111\/jvim.16409 (2022).","journal-title":"J. Vet. Intern. Med."},{"key":"2060_CR76","doi-asserted-by":"publisher","first-page":"e62879","DOI":"10.1371\/journal.pone.0062879","volume":"8","author":"P Kachroo","year":"2013","unstructured":"Kachroo, P. et al. Age-related changes following in vitro stimulation with Rhodococcus equi of peripheral blood leukocytes from neonatal foals. PLoS One. 8, e62879. https:\/\/doi.org\/10.1371\/journal.pone.0062879 (2013).","journal-title":"PLoS One"},{"key":"2060_CR77","doi-asserted-by":"publisher","first-page":"7110","DOI":"10.4049\/jimmunol.1100001","volume":"186","author":"R Blomgran","year":"2011","unstructured":"Blomgran, R. & Ernst, J. D. Lung neutrophils facilitate activation of Naive antigen-specific CD4\u2009+\u2009T cells during Mycobacterium tuberculosis infection. J. Immunol. 186, 7110\u20137119. https:\/\/doi.org\/10.4049\/jimmunol.1100001 (2011).","journal-title":"J. Immunol."},{"key":"2060_CR78","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1016\/j.imlet.2022.04.007","volume":"247","author":"D Polak","year":"2022","unstructured":"Polak, D. & Bohle, B. Neutrophils-typical atypical antigen presenting cells? Immunol. Lett. 247, 52\u201358. https:\/\/doi.org\/10.1016\/j.imlet.2022.04.007 (2022).","journal-title":"Immunol. Lett."},{"key":"2060_CR79","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1128\/cdli.10.3.345-351.2003","volume":"10","author":"KE Hooper-McGrevy","year":"2003","unstructured":"Hooper-McGrevy, K. E., Wilkie, B. N. & Prescott, J. F. Immunoglobulin G subisotype responses of pneumonic and healthy, exposed foals and adult horses to Rhodococcus equi virulence-associated proteins. Clin. Diag Lab. Immunol. 10, 345\u2013351. https:\/\/doi.org\/10.1128\/cdli.10.3.345-351.2003 (2003).","journal-title":"Clin. Diag Lab. Immunol."},{"key":"2060_CR80","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/j.1574-695X.1999.tb01258.x","volume":"24","author":"S Takai","year":"1999","unstructured":"Takai, S., Kobayashi, C., Murakami, K., Sasaki, Y. & Tsubaki, S. Live virulent Rhodococcus equi, rather than killed or avirulent, elicits protective immunity to R. equi infection in mice. FEMS Immunol. Med. Microbiol. 24, 1\u20139 (1999).","journal-title":"FEMS Immunol. Med. Microbiol."},{"key":"2060_CR81","doi-asserted-by":"publisher","first-page":"eadf9706","DOI":"10.1126\/sciadv.adf9706","volume":"9","author":"MC Gomes","year":"2023","unstructured":"Gomes, M. C., Brokatzky, D., Bielecka, M. K., Wardle, F. C. & Mostowy, S. Shigella induces epigenetic reprogramming of zebrafish neutrophils. Sci. Adv. 9, eadf9706. https:\/\/doi.org\/10.1126\/sciadv.adf9706 (2023).","journal-title":"Sci. Adv."},{"key":"2060_CR82","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1016\/j.chom.2014.02.006","volume":"15","author":"A Khosravi","year":"2014","unstructured":"Khosravi, A. et al. Gut microbiota promote hematopoiesis to control bacterial infection. Cell. Host Microbe. 15, 374\u2013381. https:\/\/doi.org\/10.1016\/j.chom.2014.02.006 (2014).","journal-title":"Cell. Host Microbe"},{"key":"2060_CR83","doi-asserted-by":"publisher","first-page":"112525","DOI":"10.1016\/j.celrep.2023.112525","volume":"42","author":"TS Kapellos","year":"2023","unstructured":"Kapellos, T. S. et al. Systemic alterations in neutrophils and their precursors in early-stage chronic obstructive pulmonary disease. Cell. Rep. 42, 112525. https:\/\/doi.org\/10.1016\/j.celrep.2023.112525 (2023).","journal-title":"Cell. Rep."},{"key":"2060_CR84","doi-asserted-by":"publisher","first-page":"e66640","DOI":"10.1371\/journal.pone.0066640","volume":"8","author":"AI Bordin","year":"2013","unstructured":"Bordin, A. I. et al. Effects of administration of live or inactivated virulent Rhodococccus equi and age on the fecal microbiome of neonatal foals. PLoS One  8, e66640. https:\/\/doi.org\/10.1371\/journal.pone.0066640 (2013).","journal-title":"PLoS One"},{"key":"2060_CR85","doi-asserted-by":"publisher","first-page":"e1009888","DOI":"10.1371\/journal.ppat.1009888","volume":"17","author":"KJ Vail","year":"2021","unstructured":"Vail, K. J. et al. The opportunistic intracellular bacterial pathogen Rhodococcus equi elicits type I interferon by engaging cytosolic DNA sensing in macrophages. PLoS Pathog. 17, e1009888. https:\/\/doi.org\/10.1371\/journal.ppat.1009888 (2021).","journal-title":"PLoS Pathog"},{"key":"2060_CR86","doi-asserted-by":"publisher","first-page":"100062","DOI":"10.1016\/j.xpro.2020.100062","volume":"1","author":"AE Sullivan","year":"2020","unstructured":"Sullivan, A. E. & Santos, S. D. M. An optimized protocol for ChIP-Seq from human embryonic stem cell cultures. STAR. Protoc. 1, 100062. https:\/\/doi.org\/10.1016\/j.xpro.2020.100062 (2020).","journal-title":"STAR. Protoc."},{"key":"2060_CR87","doi-asserted-by":"publisher","first-page":"e00383","DOI":"10.1128\/iai.00383-23","volume":"92","author":"BP da Silveira","year":"2024","unstructured":"da Silveira, B. P. et al. Impact of surface receptors TLR2, CR3, and Fc\u03b3RIII on Rhodococcus equi phagocytosis and intracellular survival in macrophages. Infect. Immun. 92, e00383\u2013e00323. https:\/\/doi.org\/10.1128\/iai.00383-23 (2024).","journal-title":"Infect. Immun."},{"key":"2060_CR88","doi-asserted-by":"publisher","first-page":"e0250133","DOI":"10.1371\/journal.pone.0250133","volume":"16","author":"SK Kahn","year":"2021","unstructured":"Kahn, S. K. et al. Antibody activities in hyperimmune plasma against the Rhodococcus equi virulence-associated protein A or poly-N-acetyl glucosamine are associated with protection of foals against rhodococcal pneumonia. PLoS One. 16, e0250133. https:\/\/doi.org\/10.1371\/journal.pone.0250133 (2021).","journal-title":"PLoS One"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-02060-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-02060-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-02060-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,25]],"date-time":"2025-05-25T01:33:00Z","timestamp":1748136780000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-02060-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,25]]},"references-count":88,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["2060"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-02060-5","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2024.02.17.579919","asserted-by":"object"}]},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,25]]},"assertion":[{"value":"19 December 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 May 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 May 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"18156"}}