{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T23:45:27Z","timestamp":1793403927646,"version":"4.5.0"},"reference-count":58,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T00:00:00Z","timestamp":1756771200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T00:00:00Z","timestamp":1756771200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100023561","name":"Ministerio de Universidades","doi-asserted-by":"publisher","award":["PID2019-107298RB-C21\/AEI\/10.13039\/ 501100011033"],"award-info":[{"award-number":["PID2019-107298RB-C21\/AEI\/10.13039\/ 501100011033"]}],"id":[{"id":"10.13039\/501100023561","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Vet Res"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>\u03b2-defensins are multifunctional peptides of the host immune system involved in responses to infectious diseases. We investigated the potential of five recombinant proteins based on bovine \u03b2-defensins (bovine neutrophil \u03b2-defensins (BNBD) 1, 2, 3, and 4, and the tracheal antimicrobial peptide (TAP)) in functions relevant to sepsis such as antimicrobial activity, lipopolysaccharide (LPS) binding and neutralisation, and the stimulation of cytokine response in epithelial cells. These \u03b2-defensins were produced in <jats:italic>Lactococcus lactis<\/jats:italic> as fusion proteins. Antimicrobial activity was tested against <jats:italic>Escherichia coli<\/jats:italic>; LPS binding and neutralisation were assessed using a fluorescent probe displacement assay and by measuring tumour necrosis factor alpha (TNF\u03b1) levels in whole blood after an LPS challenge, respectively. Interleukin-8 (IL-8) levels were quantified to evaluate the epithelial immune response. All \u03b2-defensins exhibited different properties, suggesting they may have distinct mechanisms and functions in resolving infections. The recombinant BNBD4 showed potent antimicrobial activity against <jats:italic>E. coli<\/jats:italic>, whereas TAP was more notable for its ability to bind and neutralise LPS. These findings suggest that \u03b2-defensins, particularly BNBD4 and TAP, may be utilised to treat sepsis by targeting bacterial pathogens and modulating inflammatory responses.<\/jats:p>","DOI":"10.1186\/s13567-025-01601-0","type":"journal-article","created":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T06:49:33Z","timestamp":1756795773000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Exploring the therapeutic potential of recombinant bovine \u03b2-defensins for antimicrobial and anti-inflammatory functions in sepsis management"],"prefix":"10.1186","volume":"56","author":[{"given":"Cristina","family":"Saubi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo","family":"Balt\u00e0-Foix","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose Vicente","family":"Carratal\u00e1","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesc","family":"F\u00e0bregas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Sand\u00edn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Torrent","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Garcia-Fruit\u00f3s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7830-888X","authenticated-orcid":false,"given":"Anna","family":"Ar\u00eds","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,9,2]]},"reference":[{"key":"1601_CR1","doi-asserted-by":"publisher","first-page":"3952","DOI":"10.1073\/pnas.88.9.3952","volume":"88","author":"G Diamond","year":"1991","unstructured":"Diamond G, Zasloff M, Eck H, Brasseur M, Maloy WL, Bevins CL (1991) Tracheal antimicrobial peptide, a cysteine-rich peptide from mammalian tracheal mucosa: peptide isolation and cloning of a cDNA. Proc Natl Acad Sci U S A 88:3952\u20133956. https:\/\/doi.org\/10.1073\/pnas.88.9.3952","journal-title":"Proc Natl Acad Sci U S A"},{"key":"1601_CR2","doi-asserted-by":"publisher","first-page":"6641","DOI":"10.1016\/s0021-9258(18)53298-1","volume":"268","author":"ME Selsted","year":"1993","unstructured":"Selsted ME, Tang YQ, Morris WL, McGuire PA, Novotny MJ, Smith W, Henschen AH, Cullor JS (1993) Purification, primary structures, and antibacterial activities of beta-defensins, a new family of antimicrobial peptides from bovine neutrophils. J Biol Chem 268:6641\u20136648. https:\/\/doi.org\/10.1016\/s0021-9258(18)53298-1","journal-title":"J Biol Chem"},{"key":"1601_CR3","doi-asserted-by":"publisher","first-page":"1673","DOI":"10.3389\/fimmu.2019.01673","volume":"10","author":"C Huang","year":"2019","unstructured":"Huang C, Yang X, Huang J, Liu X, Yang X, Jin H, Huang Q, Li L, Zhou R (2019) Porcine beta-defensin 2 provides protection against bacterial infection by a direct bactericidal activity and alleviates inflammation via interference with the TLR4\/NF-\u03baB pathway. Front Immunol 10:1673. https:\/\/doi.org\/10.3389\/fimmu.2019.01673","journal-title":"Front Immunol"},{"key":"1601_CR4","doi-asserted-by":"publisher","first-page":"1701","DOI":"10.1096\/fj.05-4970fje","volume":"20","author":"D Motzkus","year":"2006","unstructured":"Motzkus D, Schulz-Maronde S, Heitland A, Schulz A, Forssmann W-G, J\u00fcbner M, Maronde E (2006) The novel \u03b2-defensin DEFB123 prevents lipopolysaccharide-mediated effects in vitro and in vivo. FASEB J 20:1701\u20131702. https:\/\/doi.org\/10.1096\/fj.05-4970fje","journal-title":"FASEB J"},{"key":"1601_CR5","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1186\/s12866-016-0828-y","volume":"16","author":"M Yang","year":"2016","unstructured":"Yang M, Zhang C, Zhang X, Zhang MZ, Rottinghaus GE, Zhang S (2016) Structure-function analysis of avian \u03b2-defensin-6 and \u03b2-defensin-12: Role of charge and disulfide bridges. BMC Microbiol 16:210. https:\/\/doi.org\/10.1186\/s12866-016-0828-y","journal-title":"BMC Microbiol"},{"key":"1601_CR6","doi-asserted-by":"publisher","first-page":"2333","DOI":"10.3389\/fimmu.2019.02333","volume":"10","author":"K Xie","year":"2019","unstructured":"Xie K, Xie H, Su G, Chen D, Yu B, Mao X, Huang Z, Yu J, Luo J, Zheng P, Luo Y, He J (2019) \u0392-defensin 129 attenuates bacterial endotoxin-induced inflammation and intestinal epithelial cell apoptosis. Front Immunol 10:2333. https:\/\/doi.org\/10.3389\/fimmu.2019.02333","journal-title":"Front Immunol"},{"key":"1601_CR7","doi-asserted-by":"publisher","first-page":"12270","DOI":"10.1074\/jbc.M112.411884","volume":"288","author":"H Yu","year":"2013","unstructured":"Yu H, Dong J, Gu Y, Liu H, Xin A, Shi H, Sun F, Zhang Y, Lin D, Diao H (2013) The novel human \u03b2-defensin 114 regulates lipopolysaccharide (LPS)-mediated inflammation and protects sperm from motility loss. J Biol Chem 288:12270\u201312282. https:\/\/doi.org\/10.1074\/jbc.M112.411884","journal-title":"J Biol Chem"},{"key":"1601_CR8","doi-asserted-by":"publisher","first-page":"3395","DOI":"10.1007\/s00253-012-4588-9","volume":"97","author":"H Liu","year":"2013","unstructured":"Liu H, Yu H, Gu Y, Xin A, Zhang Y, Diao H, Lin D (2013) Human beta-defensin DEFB126 is capable of inhibiting LPS-mediated inflammation. Appl Microbiol Biotechnol 97:3395\u20133408. https:\/\/doi.org\/10.1007\/s00253-012-4588-9","journal-title":"Appl Microbiol Biotechnol"},{"key":"1601_CR9","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1016\/J.INTIMP.2005.08.008","volume":"6","author":"Y Koyama","year":"2006","unstructured":"Koyama Y, Motobu M, Hikosaka K, Yamada M, Nakamura K, Saido-Sakanaka H, Asaoka A, Yamakawa M, Sekikawa K, Kitani H, Shimura K, Nakai Y, Hirota Y (2006) Protective effects of antimicrobial peptides derived from the beetle Allomyrina dichotoma defensin on endotoxic shock in mice. Int Immunopharmacol 6:234\u2013240. https:\/\/doi.org\/10.1016\/J.INTIMP.2005.08.008","journal-title":"Int Immunopharmacol"},{"key":"1601_CR10","doi-asserted-by":"publisher","first-page":"5156","DOI":"10.1073\/pnas.93.10.5156","volume":"93","author":"G Diamond","year":"1996","unstructured":"Diamond G, Russell JP, Bevins CL (1996) Inducible expression of an antibiotic peptide gene in lipopolysaccharide-challenged tracheal epithelial cells. Proc Natl Acad Sci U S A 93:5156\u20135160. https:\/\/doi.org\/10.1073\/pnas.93.10.5156","journal-title":"Proc Natl Acad Sci U S A"},{"key":"1601_CR11","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1016\/j.vetimm.2012.09.042","volume":"151","author":"A Chapwanya","year":"2013","unstructured":"Chapwanya A, Meade KG, Doherty ML, Callanan JJ, O\u2019Farrelly C (2013) Endometrial epithelial cells are potent producers of tracheal antimicrobial peptide and serum amyloid A3 gene expression in response to E. coli stimulation. Vet Immunol Immunopathol 151:157\u2013162. https:\/\/doi.org\/10.1016\/j.vetimm.2012.09.042","journal-title":"Vet Immunol Immunopathol"},{"key":"1601_CR12","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1007\/s11259-020-09775-y","volume":"44","author":"M Boylan","year":"2020","unstructured":"Boylan M, O\u2019Brien MB, Beynon C, Meade KG (2020) 1,25(OH)D vitamin D promotes NOS2 expression in response to bacterial and viral PAMPs in primary bovine salivary gland fibroblasts. Vet Res Commun 44:83\u201388. https:\/\/doi.org\/10.1007\/s11259-020-09775-y","journal-title":"Vet Res Commun"},{"key":"1601_CR13","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1051\/vetres:2007057","volume":"39","author":"W Petzl","year":"2008","unstructured":"Petzl W, Zerbe H, G\u00fcnther J, Yang W, Seyfert H-M, N\u00fcrnberg G, Schuberth HJ (2008) Escherichia coli, but not Staphylococcus aureus triggers an early increased expression of factors contributing to the innate immune defense in the udder of the cow. Vet Res 39:18. https:\/\/doi.org\/10.1051\/vetres:2007057","journal-title":"Vet Res"},{"key":"1601_CR14","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1051\/vetres\/2009014","volume":"40","author":"J G\u00fcnther","year":"2009","unstructured":"G\u00fcnther J, Koczan D, Yang W, N\u00fcrnberg G, Repsilber D, Schuberth HJ, Park Z, Maqbool N, Molenaar A, Seyfert HM (2009) Assessment of the immune capacity of mammary epithelial cells: comparison with mammary tissue after challenge with Escherichia coli. Vet Res 40:31. https:\/\/doi.org\/10.1051\/vetres\/2009014","journal-title":"Vet Res"},{"key":"1601_CR15","doi-asserted-by":"publisher","first-page":"5706","DOI":"10.3168\/jds.2018-16141","volume":"102","author":"MF Kweh","year":"2019","unstructured":"Kweh MF, Merriman KE, Nelson CD (2019) Short communication: Inhibition of DNA methyltransferase and histone deacetylase increases \u03b2-defensin expression but not the effects of lipopolysaccharide or 1,25-dihydroxyvitamin D 3 in bovine mammary epithelial cells. J Dairy Sci 102:5706\u20135712. https:\/\/doi.org\/10.3168\/jds.2018-16141","journal-title":"J Dairy Sci"},{"key":"1601_CR16","doi-asserted-by":"publisher","first-page":"2204","DOI":"10.3389\/fvets.2023.1154386","volume":"10","author":"S Neumann","year":"2023","unstructured":"Neumann S, Siegert S, Fischer A (2023) \u03b2-defensin-4 as an endogenous biomarker in cows with mastitis. Front Vet Sci 10:2204. https:\/\/doi.org\/10.3389\/fvets.2023.1154386","journal-title":"Front Vet Sci"},{"key":"1601_CR17","doi-asserted-by":"publisher","first-page":"21535","DOI":"10.1038\/s41598-020-78752-x","volume":"10","author":"M Larz\u00e1bal","year":"2020","unstructured":"Larz\u00e1bal M, Da Silva WM, Multani A, Vagnoni LE, Moore D, Marin MS, Riviere NA, Delgado FO, Vilte DA, Victorica MR, Ma T, Le Guan L, Talia P, Cataldi A, Cobo ER (2020) Early immune innate hallmarks and microbiome changes across the gut during Escherichia coli O157: H7 infection in cattle. Sci Rep 10:21535. https:\/\/doi.org\/10.1038\/s41598-020-78752-x","journal-title":"Sci Rep"},{"key":"1601_CR18","doi-asserted-by":"publisher","first-page":"R19","DOI":"10.1186\/cc5694","volume":"11","author":"M Book","year":"2007","unstructured":"Book M, Chen Q, Lehmann LE, Klaschik S, Weber S, Schewe JC, Luepertz M, Hoeft A, Stuber F (2007) Inducibility of the endogenous antibiotic peptide \u03b2-defensin 2 is impaired in patients with severe sepsis. Crit Care 11:R19. https:\/\/doi.org\/10.1186\/cc5694","journal-title":"Crit Care"},{"key":"1601_CR19","doi-asserted-by":"publisher","first-page":"9804","DOI":"10.1021\/bi050272k","volume":"44","author":"E Kl\u00fcver","year":"2005","unstructured":"Kl\u00fcver E, Schulz-Maronde S, Scheid S, Meyer B, Forssmann WG, Adermann K (2005) Structure-activity relation of human \u03b2-defensin 3: influence of disulfide bonds and cysteine substitution on antimicrobial activity and cytotoxicity. Biochemistry 44:9804\u20139816. https:\/\/doi.org\/10.1021\/bi050272k","journal-title":"Biochemistry"},{"key":"1601_CR20","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1186\/s12934-022-01991-2","volume":"21","author":"R Roca-Pinilla","year":"2022","unstructured":"Roca-Pinilla R, Lisowski L, Ar\u00eds A, Garcia-Fruit\u00f3s E (2022) The future of recombinant host defense peptides. Microb Cell Fact 21:267. https:\/\/doi.org\/10.1186\/s12934-022-01991-2","journal-title":"Microb Cell Fact"},{"issue":"1","key":"1601_CR21","doi-asserted-by":"publisher","first-page":"1464","DOI":"10.1038\/s41467-023-37003-z","volume":"14","author":"S Chaudhary","year":"2023","unstructured":"Chaudhary S, Ali Z, Tehseen M, Haney EF, Pantoja-Angles A, Alshehri S, Wang T, Clancy GJ, Ayach M, Hauser C, Hong PY, Hamdan SM, Hancock REW, Mahfouz M (2023) Efficient in planta production of amidated antimicrobial peptides that are active against drug-resistant ESKAPE pathogens. Nat Commun 14:1464. https:\/\/doi.org\/10.1038\/s41467-023-37003-z","journal-title":"Nat Commun"},{"key":"1601_CR22","doi-asserted-by":"publisher","first-page":"815","DOI":"10.1016\/j.jare.2015.12.003","volume":"7","author":"S Aghaei","year":"2016","unstructured":"Aghaei S, Saffar B, Ghaedi K, Mobini Dehkordi M (2016) Functional analysis of recombinant codon-optimized bovine neutrophil \u03b2-defensin. J Adv Res 7:815\u2013821. https:\/\/doi.org\/10.1016\/j.jare.2015.12.003","journal-title":"J Adv Res"},{"key":"1601_CR23","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1007\/s11033-010-0125-z","volume":"38","author":"J Wu","year":"2011","unstructured":"Wu J, Wang C, He H, Hu G, Yang H, Gao Y, Zhong J (2011) Molecular analysis and recombinant expression of bovine neutrophil \u03b2-defensin 12 and its antimicrobial activity. Mol Biol Rep 38:429\u2013436. https:\/\/doi.org\/10.1007\/s11033-010-0125-z","journal-title":"Mol Biol Rep"},{"key":"1601_CR24","doi-asserted-by":"publisher","DOI":"10.1186\/s12934-022-01803-7","volume":"21","author":"A L\u00f3pez-Cano","year":"2022","unstructured":"L\u00f3pez-Cano A, Mart\u00ednez-Miguel M, Guasch J, Ratera I, Ar\u00eds A, Garcia-Fruit\u00f3s E (2022) Exploring the impact of the recombinant Escherichia coli strain on defensins antimicrobial activity: BL21 versus Origami strain. Microb Cell Fact 21:77. https:\/\/doi.org\/10.1186\/s12934-022-01803-7","journal-title":"Microb Cell Fact"},{"key":"1601_CR25","doi-asserted-by":"publisher","first-page":"1823","DOI":"10.1007\/s10096-014-2152-5","volume":"33","author":"J Kang","year":"2014","unstructured":"Kang J, Zhao D, Lyu Y, Tian L, Yin X, Yang L, Teng K, Zhou X (2014) Antimycobacterial activity of Pichia pastoris-derived mature bovine neutrophil \u03b2-defensins 5. Eur J Clin Microbiol Infect Dis 33:1823\u20131834. https:\/\/doi.org\/10.1007\/s10096-014-2152-5","journal-title":"Eur J Clin Microbiol Infect Dis"},{"key":"1601_CR26","first-page":"330","volume":"15","author":"HJ Choi","year":"2005","unstructured":"Choi HJ, Seo MJ, Lee JC, Cheigh CI, Park H, Ahn C, Pyun YR (2005) Heterologous expression of human \u03b2-defensin-1 in bacteriocin-producing Lactococcus lactis. J Microbiol Biotechnol 15:330\u2013336","journal-title":"J Microbiol Biotechnol"},{"key":"1601_CR27","doi-asserted-by":"publisher","first-page":"1833","DOI":"10.1007\/s12602-021-09847-8","volume":"13","author":"T Wang","year":"2021","unstructured":"Wang T, Wang Z, Mi J, Wang W, Li K, Qi X, Gao Y, Gao L, Liu C, Zhang Y, Pan Q, Wang X, Cui H (2021) Recombinant avian \u03b2-defensin produced by food-grade Lactococcus as a novel and potent immunological enhancer adjuvant for avian vaccine. Probiotics Antimicrob Proteins 13:1833\u20131846. https:\/\/doi.org\/10.1007\/s12602-021-09847-8","journal-title":"Probiotics Antimicrob Proteins"},{"key":"1601_CR28","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1186\/s13054-023-04690-5","volume":"27","author":"JA Kellum","year":"2023","unstructured":"Kellum JA, Ronco C (2023) The role of endotoxin in septic shock. Crit Care 27:400. https:\/\/doi.org\/10.1186\/s13054-023-04690-5","journal-title":"Crit Care"},{"key":"1601_CR29","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1001\/jama.2016.0287","volume":"315","author":"M Singer","year":"2016","unstructured":"Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, Hotchkiss RS, Levy MM, Marshall JC, Martin GS, Opal SM, Rubenfeld GD, van der Poll T, Vincent JL, Angus DC (2016) The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA 315:801\u2013810. https:\/\/doi.org\/10.1001\/jama.2016.0287","journal-title":"JAMA"},{"key":"1601_CR30","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1111\/j.1939-1676.1999.tb01134.x","volume":"13","author":"J Lofstedt","year":"1999","unstructured":"Lofstedt J, Dohoo IR, Duizer G (1999) Model to predict septicemia in diarrheic calves. J Vet Intern Med 13:81\u201388. https:\/\/doi.org\/10.1111\/j.1939-1676.1999.tb01134.x","journal-title":"J Vet Intern Med"},{"key":"1601_CR31","doi-asserted-by":"publisher","first-page":"1324","DOI":"10.2460\/javma.1993.203.09.1324","volume":"203","author":"BM Aldridge","year":"1993","unstructured":"Aldridge BM, Garry FB, Adams R (1993) Neonatal septicemia in calves: 25 cases (1985\u20131990). J Am Vet Med Assoc 203:1324\u20131329","journal-title":"J Am Vet Med Assoc"},{"key":"1601_CR32","first-page":"56","volume":"33","author":"H Hariharan","year":"1992","unstructured":"Hariharan H, Bryenton J, St Onge J, Heaney S (1992) Blood cultures from calves and foals. Can Vet J 33:56\u201357","journal-title":"Can Vet J"},{"key":"1601_CR33","first-page":"101","volume":"38","author":"G Fecteau","year":"1997","unstructured":"Fecteau G, Par\u00e9 J, Van Metre DC, Smith BP, Holmberg CA, Guterbock W, Jang S (1997) Use of a clinical sepsis score for predicting bacteremia in neonatal dairy calves on a calf rearing farm. Can Vet J 38:101\u2013104","journal-title":"Can Vet J"},{"key":"1601_CR34","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1111\/jvim.16607","volume":"37","author":"ML Pas","year":"2023","unstructured":"Pas ML, Bokma J, Lowie T, Boyen F, Pardon B (2023) Sepsis and survival in critically ill calves: risk factors and antimicrobial use. J Vet Intern Med 37:374\u2013389. https:\/\/doi.org\/10.1111\/jvim.16607","journal-title":"J Vet Intern Med"},{"key":"1601_CR35","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1159\/000515740","volume":"13","author":"RS Gabarin","year":"2021","unstructured":"Gabarin RS, Li M, Zimmel PA, Marshall JC, Li Y, Zhang H (2021) Intracellular and extracellular lipopolysaccharide signaling in sepsis: avenues for novel therapeutic strategies. J Innate Immun 13:323\u2013332. https:\/\/doi.org\/10.1159\/000515740","journal-title":"J Innate Immun"},{"key":"1601_CR36","doi-asserted-by":"publisher","first-page":"524","DOI":"10.1097\/shk.0b013e31805363c6","volume":"28","author":"DJ Klein","year":"2007","unstructured":"Klein DJ, Derzko A, Foster D, Seely AJE, Brunet F, Romaschin AD, Marshall JC (2007) Daily variation in endotoxin levels is associated with increased organ failure in critically ill patients. Shock 28:524\u2013529. https:\/\/doi.org\/10.1097\/shk.0b013e31805363c6","journal-title":"Shock"},{"key":"1601_CR37","doi-asserted-by":"publisher","first-page":"1452","DOI":"10.2527\/jas.2011-4627","volume":"90","author":"V Mani","year":"2012","unstructured":"Mani V, Weber TE, Baumgard LH, Gabler NK (2012) Growth and development symposium: endotoxin, inflammation, and intestinal function in livestock. J Anim Sci 90:1452\u20131465. https:\/\/doi.org\/10.2527\/jas.2011-4627","journal-title":"J Anim Sci"},{"key":"1601_CR38","doi-asserted-by":"publisher","first-page":"5967","DOI":"10.3168\/jds.2015-10727","volume":"99","author":"EF Eckel","year":"2016","unstructured":"Eckel EF, Ametaj BN (2016) Role of bacterial endotoxins in the etiopathogenesis of periparturient diseases of transition dairy cows. J Dairy Sci 99:5967\u20135990. https:\/\/doi.org\/10.3168\/jds.2015-10727","journal-title":"J Dairy Sci"},{"key":"1601_CR39","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1002\/evan.21887","volume":"30","author":"JF Brinkworth","year":"2021","unstructured":"Brinkworth JF, Valizadegan N (2021) Sepsis and the evolution of human increased sensitivity to lipopolysaccharide. Evol Anthropol 30:141\u2013157. https:\/\/doi.org\/10.1002\/evan.21887","journal-title":"Evol Anthropol"},{"key":"1601_CR40","doi-asserted-by":"publisher","first-page":"6225","DOI":"10.3168\/jds.2023-24350","volume":"107","author":"J Opgenorth","year":"2024","unstructured":"Opgenorth J, Mayorga EJ, Abeyta MA, Goetz BM, Rodriguez-Jimenez S, Freestone AD, McGill JL, Baumgard LH (2024) Intravenous lipopolysaccharide challenge in early- versus mid-lactation dairy cattle. I: the immune and inflammatory responses. J Dairy Sci 107:6225\u20136239. https:\/\/doi.org\/10.3168\/jds.2023-24350","journal-title":"J Dairy Sci"},{"key":"1601_CR41","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1016\/j.vetimm.2014.11.005","volume":"163","author":"E Plessers","year":"2015","unstructured":"Plessers E, Wyns H, Watteyn A, Pardon B, De Backer P, Croubels S (2015) Characterization of an intravenous lipopolysaccharide inflammation model in calves with respect to the acute-phase response. Vet Immunol Immunopathol 163:46\u201356. https:\/\/doi.org\/10.1016\/j.vetimm.2014.11.005","journal-title":"Vet Immunol Immunopathol"},{"key":"1601_CR42","doi-asserted-by":"publisher","unstructured":"Yilmaz Z, Eralp Inan O, Kocaturk M, Baykal AT, Hacariz O, Hatipoglu I, Tvarijonaviciute A, Cansev M, Ceron J, Ulus IH (2016) Changes in serum proteins after endotoxin administration in healthy and choline-treated calves. BMC Vet Res 12:210. https:\/\/doi.org\/10.1186\/s12917-016-0837-y","DOI":"10.1186\/s12917-016-0837-y"},{"key":"1601_CR43","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/j.cvfa.2021.11.006","volume":"38","author":"D Renaud","year":"2022","unstructured":"Renaud D, Pardon B (2022) Preparing male dairy calves for the veal and dairy beef industry. Vet Clin North Am Food Anim Pract 38:77\u201392. https:\/\/doi.org\/10.1016\/j.cvfa.2021.11.006","journal-title":"Vet Clin North Am Food Anim Pract"},{"key":"1601_CR44","doi-asserted-by":"publisher","first-page":"9304","DOI":"10.3168\/JDS.2023-23374","volume":"106","author":"L Pisoni","year":"2023","unstructured":"Pisoni L, Devant M, Bassols AM, Saco Y, Pato R, Pujols J, Marti S (2023) The effects of colostrum consumption and feed restriction during marketing and transportation of male dairy beef calves: impact on pre-transport nutritional status and on farm recovery. J Dairy Sci 106:9304\u20139322. https:\/\/doi.org\/10.3168\/JDS.2023-23374","journal-title":"J Dairy Sci"},{"key":"1601_CR45","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1016\/S1473-3099(07)70265-7","volume":"8","author":"T van der Poll","year":"2008","unstructured":"van der Poll T, Opal SM (2008) Host-pathogen interactions in sepsis. Lancet Infect Dis 8:32\u201343. https:\/\/doi.org\/10.1016\/S1473-3099(07)70265-7","journal-title":"Lancet Infect Dis"},{"key":"1601_CR46","unstructured":"Balt\u00e0-Foix R (2023) Study of innate immunity-related proteins for the treatment of bovine infectious diseases. PhD Thesis, Universitat Aut\u00f2noma de Barcelona, Program in Biochemistry, Molecular Biology and Biomedicine http:\/\/hdl.handle.net\/10803\/691064"},{"key":"1601_CR47","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1186\/s12934-014-0167-3","volume":"13","author":"O Cano-Garrido","year":"2014","unstructured":"Cano-Garrido O, Rueda FL, S\u00e0nchez-Garc\u00eda L, Ruiz-\u00c1vila L, Bosser R, Villaverde A, Garc\u00eda-Fruit\u00f3s E (2014) Expanding the recombinant protein quality in Lactococcus lactis. Microb Cell Fact 13:167. https:\/\/doi.org\/10.1186\/s12934-014-0167-3","journal-title":"Microb Cell Fact"},{"key":"1601_CR48","doi-asserted-by":"publisher","first-page":"23798","DOI":"10.1038\/s41598-021-03220-z","volume":"11","author":"R Roca-Pinilla","year":"2021","unstructured":"Roca-Pinilla R, Holani R, L\u00f3pez-Cano A, Saubi C, Balt\u00e0-Foix R, Cobo ER, Garcia-Fruit\u00f3s E, Ar\u00eds A (2021) Sequence edition of single domains modulates the final immune and antimicrobial potential of a new generation of multidomain recombinant proteins. Sci Rep 11:23798. https:\/\/doi.org\/10.1038\/s41598-021-03220-z","journal-title":"Sci Rep"},{"key":"1601_CR49","doi-asserted-by":"publisher","first-page":"e14483","DOI":"10.1111\/1751-7915.14483","volume":"17","author":"JV Carratal\u00e1","year":"2024","unstructured":"Carratal\u00e1 JV, Ferrer-Miralles N, Garcia-Fruit\u00f3s E, Ar\u00eds A (2024) LysJEP8: a promising novel endolysin for combating multidrug-resistant Gram-negative bacteria. Microb Biotechnol 17:e14483. https:\/\/doi.org\/10.1111\/1751-7915.14483","journal-title":"Microb Biotechnol"},{"key":"1601_CR50","doi-asserted-by":"publisher","unstructured":"Sand\u00edn D, Valle J, Chaves-Arquero B, Prats-Ejarque G, Larrosa MN, Gonz\u00e1lez-L\u00f3pez JJ, Jim\u00e9nez MA, Boix E, Andreu D (2021)\u00a0Rationally Modified Antimicrobial Peptides from the N\u2011Terminal Domain of Human RNase 3 Show Exceptional Serum Stability.\u00a0\u00a0Journal of Medicinal Chemistry 64(15). https:\/\/doi.org\/10.1021\/acs.jmedchem.1c00795","DOI":"10.1021\/acs.jmedchem.1c00795"},{"key":"1601_CR51","doi-asserted-by":"publisher","first-page":"840","DOI":"10.1016\/j.bbrc.2007.03.149","volume":"357","author":"H Diao","year":"2007","unstructured":"Diao H, Guo C, Lin D, Zhang Y (2007) Intein-mediated expression is an effective approach in the study of \u03b2-defensins. Biochem Biophys Res Commun 357:840\u2013846. https:\/\/doi.org\/10.1016\/j.bbrc.2007.03.149","journal-title":"Biochem Biophys Res Commun"},{"key":"1601_CR52","doi-asserted-by":"publisher","first-page":"466","DOI":"10.1189\/jlb.0804452","volume":"77","author":"H-G Sahl","year":"2004","unstructured":"Sahl H-G, Pag U, Bonness S, Wagner S, Antcheva N, Tossi A (2004) Mammalian defensins: structures and mechanism of antibiotic activity. J Leukoc Biol 77:466\u2013475. https:\/\/doi.org\/10.1189\/jlb.0804452","journal-title":"J Leukoc Biol"},{"key":"1601_CR53","doi-asserted-by":"publisher","first-page":"9307","DOI":"10.1021\/bi034403y","volume":"42","author":"V Krishnakumari","year":"2003","unstructured":"Krishnakumari V, Sharadadevi A, Singh S, Nagaraj R (2003) Single disulfide and linear analogues corresponding to the carboxy-terminal segment of bovine \u03b2-defensin-2: effects of introducing the \u03b2-hairpin nucleating sequence D-pro-gly on antibacterial activity and biophysical properties. Biochemistry 42:9307\u20139315. https:\/\/doi.org\/10.1021\/bi034403y","journal-title":"Biochemistry"},{"key":"1601_CR54","doi-asserted-by":"publisher","first-page":"170438","DOI":"10.1016\/j.peptides.2020.170438","volume":"136","author":"J Hou","year":"2021","unstructured":"Hou J, Liu H, Diao H, Yu H (2021) The truncated human beta-defensin 118 can modulate lipopolysaccharide mediated inflammatory response in RAW264.7 macrophages. Peptides 136:170438. https:\/\/doi.org\/10.1016\/j.peptides.2020.170438","journal-title":"Peptides"},{"key":"1601_CR55","doi-asserted-by":"publisher","first-page":"1073","DOI":"10.1002\/eji.200940041","volume":"40","author":"F Semple","year":"2010","unstructured":"Semple F, Webb S, Li HN, Patel HB, Perretti M, Jackson IJ, Gray M, Davidson DJ, Dorin JR (2010) Human \u03b2-defensin 3 has immunosuppressive activity in vitro and in vivo. Eur J Immunol 40:1073\u20131078. https:\/\/doi.org\/10.1002\/eji.200940041","journal-title":"Eur J Immunol"},{"key":"1601_CR56","doi-asserted-by":"publisher","first-page":"3478","DOI":"10.4049\/jimmunol.146.10.3478","volume":"146","author":"KJ Van Zee","year":"1991","unstructured":"Van Zee KJ, DeForge LE, Fischer E, Marano MA, Kenney JS, Remick DG, Lowry SF, Moldawer LL (1991) IL-8 in septic shock, endotoxemia, and after IL-1 administration. J Immunol 146:3478\u20133482","journal-title":"J Immunol"},{"key":"1601_CR57","doi-asserted-by":"publisher","first-page":"1126874","DOI":"10.3389\/fimmu.2023.1126874","volume":"14","author":"H Tang","year":"2023","unstructured":"Tang H, Qin S, Li Z, Gao W, Tang M, Dong X (2023) Early immune system alterations in patients with septic shock. Front Immunol 14:1126874. https:\/\/doi.org\/10.3389\/fimmu.2023.1126874","journal-title":"Front Immunol"},{"key":"1601_CR58","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1385\/1-59259-890-0:571","volume-title":"The proteomics protocols handbook","author":"E Gasteiger","year":"2005","unstructured":"Gasteiger E, Hoogland C, Gattiker A, Duvaud S, Wilkins MR, Appel RD, Bairoch A (2005) Protein identification and analysis tools on the ExPASy server. In: Walker JM (ed) The proteomics protocols handbook. Humana Press, Totowa, pp 571\u2013607"}],"container-title":["Veterinary Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13567-025-01601-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13567-025-01601-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13567-025-01601-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T04:14:44Z","timestamp":1757477684000},"score":1,"resource":{"primary":{"URL":"https:\/\/veterinaryresearch.biomedcentral.com\/articles\/10.1186\/s13567-025-01601-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,2]]},"references-count":58,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["1601"],"URL":"https:\/\/doi.org\/10.1186\/s13567-025-01601-0","relation":{},"ISSN":["1297-9716"],"issn-type":[{"value":"1297-9716","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,2]]},"assertion":[{"value":"12 February 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 June 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 September 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 that they have no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"173"}}