{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T07:09:48Z","timestamp":1771571388397,"version":"3.50.1"},"reference-count":85,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T00:00:00Z","timestamp":1771545600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Caprine tuberculosis (cTB) is a zoonotic disease with significant implications for animal and public health and economic impact. Therefore, accurate ante-mortem diagnosis is essential. Diagnosis in goats rely on the single and comparative intradermal tuberculin test (SITT and CITT, respectively), both of which showing limited diagnostic performance. The aim of the study was to characterize the immune and physiological responses to cTB in naturally infected goats and to identify potential\n                      <jats:italic>in vitro<\/jats:italic>\n                      biomarkers that could improve the reliability of cTB diagnosis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methodology<\/jats:title>\n                    <jats:p>\n                      The study was conducted in a cTB infected herd and goats were classified as reactors (positive to SITT or IFN-\u03b3 release assay and considered as infected) and non-reactors. Basal production of fifteen key immune cytokines was measured in plasma samples (\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f19) and compared with levels observed after stimulation with bovine purified protein derivative (PPDb). Acute phase proteins (haptoglobin\/Hp and serum amyloid-A\/SAA) and oxidative stress markers (total antioxidant status\/TAS and malondialdehyde\/MDA) were determined in serum samples (\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f90) while complete blood count (CBC) was performed on whole-blood samples (\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f44).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results and discussion<\/jats:title>\n                    <jats:p>\n                      Regarding cytokine expression patterns, plasma levels of IFN-\u03b3 and IFN-\u03b3-inducible protein 10 (IP-10) in PPDb-stimulated samples were significantly higher (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.005 and\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.001, respectively) in reactor goats than in non-reactor. When considering the difference between PPDb and PBS-stimulated samples (\u0394-cytokine), levels of \u0394-IFN-\u03b3, \u0394-IP-10 and \u0394-IL-1\u03b1 were significantly higher (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.0006,\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.0001 and\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.022, respectively) in reactor goats compared to non-reactor. In addition, significantly higher (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.014) levels of serum TAS were observed in reactor vs. non-reactor goats whereas no significant differences (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;gt;\u202f0.05) were found for Hp, SAA and MDA. Finally, among the CBC parameters, only the percentage of mid-range cells was significantly higher (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.05) in reactor vs. non-reactor goats. This study demonstrates the differential expression of immunological (IFN-\u03b3, IP-10 and IL-1\u03b1) and physiological (TAS) biomarkers in goats reacting to TB diagnostic tests and suggest their potential as biomarkers of cTB infection. These findings could lead to the development of novel diagnostic\n                      <jats:italic>in vitro<\/jats:italic>\n                      methodologies and contribute to more effective cTB eradication strategies.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmicb.2026.1765857","type":"journal-article","created":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T06:42:14Z","timestamp":1771569734000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploring specific biomarkers in blood for in vitro diagnosis of caprine tuberculosis"],"prefix":"10.3389","volume":"17","author":[{"given":"Carlos","family":"Velasco","sequence":"first","affiliation":[{"name":"VISAVET Health Surveillance Centre, Complutense University of Madrid","place":["Madrid, Spain"]},{"name":"Departamento de Sanidad Animal, Facultad de Veterinaria, Universidad Complutense de Madrid","place":["Madrid, Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alvaro","family":"Roy","sequence":"additional","affiliation":[{"name":"Centro Nacional de Epidemiolog\u00eda, Instituto de Salud Carlos III","place":["Madrid, Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fatima","family":"Cruz-Lopez","sequence":"additional","affiliation":[{"name":"VISAVET Health Surveillance Centre, Complutense University of Madrid","place":["Madrid, Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alberto","family":"Gomez-Buendia","sequence":"additional","affiliation":[{"name":"VISAVET Health Surveillance Centre, Complutense University of Madrid","place":["Madrid, Spain"]},{"name":"Departamento de Sanidad Animal, Facultad de Veterinaria, Universidad Complutense de Madrid","place":["Madrid, Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Javier","family":"Ortega","sequence":"additional","affiliation":[{"name":"VISAVET Health Surveillance Centre, Complutense University of Madrid","place":["Madrid, Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sof\u00eda","family":"Mendez-Lopez","sequence":"additional","affiliation":[{"name":"VISAVET Health Surveillance Centre, Complutense University of Madrid","place":["Madrid, Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucia","family":"de Juan","sequence":"additional","affiliation":[{"name":"VISAVET Health Surveillance Centre, Complutense University of Madrid","place":["Madrid, Spain"]},{"name":"Departamento de Sanidad Animal, Facultad de Veterinaria, Universidad Complutense de Madrid","place":["Madrid, Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucas","family":"Dominguez","sequence":"additional","affiliation":[{"name":"VISAVET Health Surveillance Centre, Complutense University of Madrid","place":["Madrid, Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beatriz","family":"Romero","sequence":"additional","affiliation":[{"name":"VISAVET Health Surveillance Centre, Complutense University of Madrid","place":["Madrid, Spain"]},{"name":"Departamento de Sanidad Animal, Facultad de Veterinaria, Universidad Complutense de Madrid","place":["Madrid, Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julio","family":"Alvarez","sequence":"additional","affiliation":[{"name":"VISAVET Health Surveillance Centre, Complutense University of Madrid","place":["Madrid, Spain"]},{"name":"Departamento de Sanidad Animal, Facultad de Veterinaria, Universidad Complutense de Madrid","place":["Madrid, Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Javier","family":"Bezos","sequence":"additional","affiliation":[{"name":"VISAVET Health Surveillance Centre, Complutense University of Madrid","place":["Madrid, Spain"]},{"name":"Departamento de Sanidad Animal, Facultad de Veterinaria, Universidad Complutense de Madrid","place":["Madrid, Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,20]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"10.3791\/61122","DOI":"10.3791\/61122","article-title":"Evaluation of oxidative stress in biological samples using the thiobarbituric acid reactive substances assay","volume":"12","author":"Aguilar Diaz De Leon","year":"2020","journal-title":"J. Vis. Exp."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"110320","DOI":"10.1016\/j.vetmic.2024.110320","article-title":"Immunological mechanisms involved in the protection against development of pulmonary tuberculosis in naturally infected goats","volume":"300","author":"Agull\u00f3-Ros","year":"2025","journal-title":"Vet. Microbiol."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.smallrumres.2018.03.011","article-title":"Antioxidant biomarkers in the milk of early postpartum Aardi goats during winter","volume":"162","author":"Al-Hassan","year":"2018","journal-title":"Small Rumin. Res."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1016\/j.vetmic.2007.08.034","article-title":"Interference of paratuberculosis with the diagnosis of tuberculosis in a goat flock with a natural mixed infection","volume":"128","author":"Alvarez","year":"2008","journal-title":"Vet. Microbiol."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"1785","DOI":"10.1099\/ijs.0.02532-0","article-title":"Elevation of Mycobacterium tuberculosis subsp. caprae Aranaz et al. 1999 to species rank as Mycobacterium caprae comb. nov., sp. nov.","volume":"53","author":"Aranaz","year":"2003","journal-title":"Int. J. Syst. Evol. Microbiol."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"10-1128","DOI":"10.1128\/microbiolspec.TNMI7-0004-2016","article-title":"Hematologic complications of tuberculosis","volume":"4","author":"Balepur","year":"2016","journal-title":"Microbiol. Spectr."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"504","DOI":"10.1515\/ap-2018-0060","article-title":"Systemic oxidative stress in Suffolk and Santa Ines sheep experimentally infected with Haemonchus contortus","volume":"63","author":"Baptistiolli","year":"2018","journal-title":"Acta Parasitol."},{"key":"ref8","first-page":"1003","article-title":"Rapid assay to evaluate the total antioxidant capacity in donkey milk and in more common animal milk for human consumption","volume":"1","author":"Beghelli","year":"2016","journal-title":"Austin Food Sci."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"104700","DOI":"10.1016\/j.prevetmed.2019.104700","article-title":"Parallel measurement of IFN-\u03b3 and IP-10 in QuantiFERON\u00ae-TB gold (QFT) plasma improves the detection of Mycobacterium bovis infection in African buffaloes (Syncerus caffer)","volume":"169","author":"Bernitz","year":"2019","journal-title":"Prev. Vet. Med."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1016\/j.rvsc.2011.05.020","article-title":"Study of peripheral blood cell populations involved in the immune response of goats naturally infected with Mycobacterium caprae","volume":"93","author":"Bezos","year":"","journal-title":"Res. Vet. Sci."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1016\/j.tvjl.2011.02.010","article-title":"Tuberculosis in goats: assessment of current in vivo cell-mediated and antibody-based diagnostic assays","volume":"191","author":"Bezos","year":"","journal-title":"Vet. J."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"S44","DOI":"10.1016\/j.rvsc.2014.04.002","article-title":"Current ante-mortem techniques for diagnosis of bovine tuberculosis","volume":"97","author":"Bezos","year":"","journal-title":"Res. Vet. Sci."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.rvsc.2013.10.007","article-title":"Evaluation of single and comparative intradermal tuberculin tests for tuberculosis eradication in caprine flocks in Castilla y Le\u00f3n (Spain)","volume":"96","author":"Bezos","year":"","journal-title":"Res. Vet. Sci."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"1396","DOI":"10.3390\/antiox13111396","article-title":"Oxidative stress in canine diseases: a comprehensive review","volume":"13","author":"Blanca","year":"2024","journal-title":"Antioxidants"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"460","DOI":"10.1111\/j.1348-0421.2009.00141.x","article-title":"Study of the immunological profile towards Mycobacterium bovis antigens in naturally infected cattle","volume":"53","author":"Blanco","year":"2009","journal-title":"Microbiol. Immunol."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.vetmic.2019.01.007","article-title":"Simultaneous measurement of antigen-induced CXCL10 and IFN-\u03b3 enhances test sensitivity for bovine TB detection in cattle","volume":"230","author":"Coad","year":"2019","journal-title":"Vet. Microbiol."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"110559","DOI":"10.1016\/j.vetimm.2023.110559","article-title":"Mycobacterium tuberculosis complex detection in rural goat herds in South Africa using Bayesian latent class analysis","volume":"257","author":"Cooke","year":"2023","journal-title":"Vet. Immunol. Immunopathol."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1016\/j.rvsc.2005.11.005","article-title":"Ante mortem diagnosis of tuberculosis in cattle: a review of the tuberculin tests, \u03b3-interferon assay and other ancillary diagnostic techniques","volume":"81","author":"De La Rua-Domenech","year":"2006","journal-title":"Res. Vet. Sci."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"1872","DOI":"10.1128\/CVI.05323-11","article-title":"Experimental model of tuberculosis in the domestic goat after endobronchial infection with Mycobacterium caprae","volume":"18","author":"de Val","year":"2011","journal-title":"Clin. Vaccine Immunol."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"106453","DOI":"10.1016\/j.tvjl.2025.106453","article-title":"Haptoglobin response in serum and pleural fluid of tuberculin reactor cattle assessed by culture and gross pathology","volume":"314","author":"Didkowska","year":"2025","journal-title":"Vet. J."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"S20","DOI":"10.1016\/j.rvsc.2014.03.017","article-title":"Pathology of bovine tuberculosis","volume":"97","author":"Domingo","year":"2014","journal-title":"Res. Vet. Sci."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.tvjl.2003.09.003","article-title":"The time is right for acute phase protein assays","volume":"168","author":"Eckersall","year":"2004","journal-title":"Vet. J."},{"key":"ref23","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/B978-0-12-370491-7.00005-2","article-title":"Proteins, proteomics, and the dysproteinemias","volume-title":"Clinical biochemistry of domestic animals","author":"Eckersall","year":"2008"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/j.tvjl.2010.04.009","article-title":"Acute phase proteins: biomarkers of infection and inflammation in veterinary medicine","volume":"185","author":"Eckersall","year":"2010","journal-title":"Vet. J."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"2975","DOI":"10.2903\/j.efsa.2012.2975","article-title":"Scientific opinion on the use of a gamma interferon test for the diagnosis of bovine tuberculosis","volume":"10","year":"2012","journal-title":"EFSA J."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"101352","DOI":"10.1016\/j.cimid.2019.101352","article-title":"Acute phase proteins, proinflammatory cytokines and oxidative stress biomarkers in sheep, goats and she-camels with Coxiella burnetii infection-induced abortion","volume":"67","author":"El-Deeb","year":"2019","journal-title":"Comp. Immunol. Microbiol. Infect. Dis."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.tube.2017.04.009","article-title":"Evaluation of antigen specific interleukin-1\u03b2 as a biomarker to detect cattle infected with Mycobacterium bovis","volume":"105","author":"Elnaggar","year":"2017","journal-title":"Tuberculosis"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1016\/j.clinbiochem.2003.11.015","article-title":"A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation","volume":"37","author":"Erel","year":"2004","journal-title":"Clin. Biochem."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1016\/j.smim.2014.09.011","article-title":"Pro- and anti-inflammatory cytokines in tuberculosis: a two-edged sword in TB pathogenesis","volume":"26","author":"Etna","year":"2014","journal-title":"Semin. Immunol."},{"key":"ref30","volume-title":"Goats population \u2013 annual data","year":"2025"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"1512571","DOI":"10.3389\/fvets.2024.1512571","article-title":"Cytokines as potential biomarkers for the diagnosis of Mycobacterium bovis infection in Mediterranean buffaloes (Bubalus bubalis)","volume":"11","author":"Franzoni","year":"2024","journal-title":"Front. Vet. Sci."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"e0163971","DOI":"10.1371\/journal.pone.0163971","article-title":"Oxidative stress in wild boars naturally and experimentally infected with Mycobacterium bovis","volume":"11","author":"Gass\u00f3","year":"2016","journal-title":"PLoS One"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"7615716","DOI":"10.1155\/2023\/7615716","article-title":"Accuracy of tests for diagnosis of animal tuberculosis: moving away from the golden calf (and towards Bayesian models)","volume":"2023","author":"Gomez-Buendia","year":"","journal-title":"Transbound. Emerg. Dis."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1186\/s13567-023-01187-5","article-title":"Evaluation of the performance of the IFN-\u03b3 release assay in bovine tuberculosis free herds from five European countries","volume":"54","author":"Gomez-Buendia","year":"","journal-title":"Vet. Res."},{"key":"ref35","doi-asserted-by":"publisher","first-page":"580","DOI":"10.1177\/104063870802000507","article-title":"Acute phase protein response in goats","volume":"20","author":"Gonz\u00e1lez","year":"2008","journal-title":"J. Vet. Diagn. Invest."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"974","DOI":"10.1128\/CVI.00324-15","article-title":"IP-10 is a sensitive biomarker of antigen recognition in whole-blood stimulation assays used for the diagnosis of Mycobacterium bovis infection in African buffaloes (Syncerus caffer)","volume":"22","author":"Goosen","year":"2015","journal-title":"Clin. Vaccine Immunol."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1051\/vetres:2004051","article-title":"Molecular characterization of Mycobacterium tuberculosis complex isolates from wild ungulates in south-Central Spain","volume":"36","author":"Gortazar","year":"2005","journal-title":"Vet. Res."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"18562","DOI":"10.1074\/jbc.M500490200","article-title":"Serum amyloid a protein binds to outer membrane protein a of gram-negative bacteria","volume":"280","author":"Hari-Dass","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref39","doi-asserted-by":"publisher","first-page":"1","DOI":"10.15547\/bjvm.1050","article-title":"Acute phase proteins in sheep and goats \u2013 function, reference ranges and assessment methods: an overview","volume":"21","author":"Iliev","year":"2018","journal-title":"Bulg. J. Vet. Med."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"110485","DOI":"10.1016\/j.vetmic.2025.110485","article-title":"Evaluation of techniques for post-mortem diagnosis of Mycobacterium tuberculosis complex infection in goats","volume":"304","author":"Jim\u00e9nez-Mart\u00edn","year":"2025","journal-title":"Vet. Microbiol."},{"key":"ref41","doi-asserted-by":"publisher","first-page":"e00551-16","DOI":"10.1128\/CVI.00551-16","article-title":"Tuberculin skin testing boosts interferon gamma responses to DIVA reagents in Mycobacterium bovis-infected cattle","volume":"24","author":"Jones","year":"2017","journal-title":"Clin. Vaccine Immunol."},{"key":"ref42","doi-asserted-by":"publisher","first-page":"1946","DOI":"10.1128\/CVI.00377-10","article-title":"Simultaneous measurement of antigen-stimulated interleukin-1 beta and gamma interferon production enhances test sensitivity for the detection of Mycobacterium bovis infection in cattle","volume":"17","author":"Jones","year":"2010","journal-title":"Clin. Vaccine Immunol."},{"key":"ref43","doi-asserted-by":"publisher","first-page":"1098","DOI":"10.1084\/jem.166.4.1098","article-title":"The expression of a gamma interferon-induced protein (IP-10) in delayed immune responses in human skin","volume":"166","author":"Kaplan","year":"1987","journal-title":"J. Exp. Med."},{"key":"ref44","doi-asserted-by":"publisher","first-page":"731878","DOI":"10.3389\/fimmu.2021.731878","article-title":"Acute phase proteins are baseline predictors of tuberculosis treatment failure","volume":"12","author":"Kumar","year":"2021","journal-title":"Front. Immunol."},{"key":"ref45","doi-asserted-by":"publisher","first-page":"6021","DOI":"10.3168\/jds.2021-21301","article-title":"Development and evaluation of a Mycobacterium bovis interferon-\u03b3 enzyme-linked immunospot (ELISpot) assay for detection of bovine tuberculosis","volume":"105","author":"Li","year":"2022","journal-title":"J. Dairy Sci."},{"key":"ref46","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1111\/j.1751-0813.1998.tb15686.x","article-title":"Evaluation of the gamma-interferon assay for eradication of tuberculosis in a goat herd","volume":"76","author":"Li\u00e9bana","year":"1998","journal-title":"Aust. Vet. J."},{"key":"ref47","doi-asserted-by":"publisher","first-page":"943","DOI":"10.3168\/jds.2024-25093","article-title":"Associations between lung consolidation and serum amyloid a and haptoglobin, and the potential of acute phase proteins to differentiate primary respiratory tract pathogens in calves","volume":"108","author":"Lowie","year":"2025","journal-title":"J. Dairy Sci."},{"key":"ref48","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1007\/978-3-319-64371-7_7","article-title":"Mycobacterium tuberculosis complex members adapted to wild and domestic animals","volume":"1019","author":"Malone","year":"2017","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref49","doi-asserted-by":"publisher","first-page":"778","DOI":"10.1016\/j.immuni.2019.03.012","article-title":"Interleukin-1 and related cytokines in the regulation of inflammation and immunity","volume":"50","author":"Mantovani","year":"2019","journal-title":"Immunity"},{"key":"ref50","doi-asserted-by":"publisher","first-page":"2200852","DOI":"10.2807\/1560-7917.ES.2023.28.12.2200852","article-title":"A one health approach revealed the long-term role of Mycobacterium caprae as the hidden cause of human tuberculosis in a region of Spain, 2003 to 2022","volume":"28","author":"Mart\u00ednez-Lirola","year":"2023","journal-title":"Euro Surveill."},{"key":"ref51","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.cyto.2013.06.002","article-title":"Interleukin-17 in veterinary animal species and its role in various diseases: a review","volume":"64","author":"Mensikova","year":"2013","journal-title":"Cytokine"},{"key":"ref52","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1177\/104063878900100304","article-title":"Serum biochemical and hematologic values of normal and Mycobacterium bovis-infected American bison","volume":"1","author":"Miller","year":"1989","journal-title":"J. Vet. Diagn. Invest."},{"key":"ref53","volume-title":"Manual para el control de la infecci\u00f3n por el CMT en establecimientos de ganado caprino incluidos en el programa nacional de erradicaci\u00f3n de la infecci\u00f3n por el complejo","year":"2024"},{"key":"ref54","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1016\/S1090-0233(03)00119-9","article-title":"Current research on acute phase proteins in veterinary diagnosis: an overview","volume":"168","author":"Murata","year":"2004","journal-title":"Vet. J."},{"key":"ref55","doi-asserted-by":"publisher","first-page":"1042428","DOI":"10.3389\/fvets.2022.1042428","article-title":"Effect of a recent parenteral dexamethasone and ketoprofen administration on the immunological diagnosis of tuberculosis in goats","volume":"9","author":"Ortega","year":"2022","journal-title":"Front. Vet. Sci."},{"key":"ref56","doi-asserted-by":"publisher","first-page":"e26254","DOI":"10.1371\/journal.pone.002625431","article-title":"Evidence for oxidative stress and defective antioxidant response in guinea pigs with tuberculosis","volume":"6","author":"Palanisamy","year":"2011","journal-title":"PLoS One"},{"key":"ref57","doi-asserted-by":"publisher","first-page":"61","DOI":"10.3390\/pathogens11010061","article-title":"The bovine tuberculoid granuloma","volume":"11","author":"Palmer","year":"2022","journal-title":"Pathogens"},{"key":"ref58","doi-asserted-by":"publisher","first-page":"109988","DOI":"10.1016\/j.vetimm.2019.109988","article-title":"Biomarkers of cell-mediated immunity to bovine tuberculosis","volume":"220","author":"Palmer","year":"2020","journal-title":"Vet. Immunol. Immunopathol."},{"key":"ref59","doi-asserted-by":"publisher","first-page":"e0155440","DOI":"10.1371\/journal.pone.0155440","article-title":"Antigen-specific IP-10 release is a sensitive biomarker of Mycobacterium bovis infection in cattle","volume":"11","author":"Parsons","year":"2016","journal-title":"PLoS One"},{"key":"ref60","doi-asserted-by":"publisher","first-page":"5064","DOI":"10.1002\/jsfa.9550","article-title":"Twenty-five years of total antioxidant capacity measurement of foods and biological fluids: merits and limitations","volume":"100","author":"Pellegrini","year":"2020","journal-title":"J. Sci. Food Agric."},{"key":"ref61","doi-asserted-by":"publisher","first-page":"100993","DOI":"10.1016\/j.onehlt.2025.100993","article-title":"Zoonotic tuberculosis in Catalonia, Spain: phylogenetic insights into Mycobacterium bovis and M. caprae transmission at the human-livestock interface","volume":"20","author":"P\u00e9rez De Val","year":"2025","journal-title":"One Health"},{"key":"ref62","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1111\/vcp.13381","article-title":"Serum total antioxidant status in dogs: reference intervals and influence of multiple biological and analytical factors","volume":"53","author":"Perez-Montero","year":"2024","journal-title":"Vet. Clin. Pathol."},{"key":"ref63","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1186\/s12917-025-04614-1","article-title":"Malondialdehyde (MDA) and 8-hydroxy-2\u2032-deoxyguanosine (8-OHdG) levels in canine serum: establishing reference intervals and influencing factors","volume":"21","author":"Perez-Montero","year":"2025","journal-title":"BMC Vet. Res."},{"key":"ref64","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1051\/vetres:2004002","article-title":"Application of acute phase protein measurements in veterinary clinical chemistry","volume":"35","author":"Petersen","year":"2004","journal-title":"Vet. Res."},{"key":"ref65","volume-title":"R. A language and environment for statistical computing","year":"2025"},{"key":"ref66","doi-asserted-by":"publisher","first-page":"105102","DOI":"10.1016\/j.prevetmed.2020.105102","article-title":"Accuracy of tuberculosis diagnostic tests in small ruminants: a systematic review and meta-analysis","volume":"182","author":"Roy","year":"2020","journal-title":"Prev. Vet. Med."},{"key":"ref67","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1111\/vcp.13220","article-title":"Acute phase proteins in cattle and swine: a review","volume":"52","author":"Saco","year":"2023","journal-title":"Vet. Clin. Pathol."},{"key":"ref68","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.vetimm.2010.02.007","article-title":"Bovine tuberculosis: effect of the tuberculin skin test on in vitro interferon gamma responses","volume":"136","author":"Schiller","year":"2010","journal-title":"Vet. Immunol. Immunopathol."},{"key":"ref69","doi-asserted-by":"publisher","first-page":"1196","DOI":"10.1128\/CVI.00150-09","article-title":"Optimization of a whole-blood gamma interferon assay for detection of Mycobacterium bovis-infected cattle","volume":"16","author":"Schiller","year":"2009","journal-title":"Clin. Vaccine Immunol."},{"key":"ref70","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1111\/j.1439-0442.2005.00703.x","article-title":"Systemic AA-amyloidosis in a European wild boar (Sus scrofa) suffering from generalized tuberculosis","volume":"52","author":"Segal\u00e9s","year":"2005","journal-title":"J. Vet. Med. A Physiol. Pathol. Clin. Med."},{"key":"ref71","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1053\/jcpa.2000.0397","article-title":"Immunophenotypical characterization of the lymphocyte infiltrate in caprine pulmonary tuberculosis","volume":"123","author":"Seva","year":"2000","journal-title":"J. Comp. Pathol."},{"key":"ref72","doi-asserted-by":"publisher","first-page":"4424","DOI":"10.4103\/jfmpc.jfmpc_2451_21","article-title":"Evaluation of hematological parameters in pulmonary tuberculosis patients","volume":"11","author":"Shah","year":"2022","journal-title":"J. Family Med. Prim. Care"},{"key":"ref73","doi-asserted-by":"publisher","first-page":"7695364","DOI":"10.1155\/2018\/7695364","article-title":"Role of oxidative stress in the pathology and management of human tuberculosis","volume":"2018","author":"Shastri","year":"2018","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref74","doi-asserted-by":"publisher","first-page":"110152","DOI":"10.1016\/j.vetimm.2020.110152","article-title":"Use of the MILLIPLEX\u00ae bovine cytokine\/chemokine multiplex assay to identify Mycobacterium bovis-infection biomarkers in African buffaloes (Syncerus caffer)","volume":"231","author":"Smith","year":"","journal-title":"Vet. Immunol. Immunopathol."},{"key":"ref75","doi-asserted-by":"publisher","first-page":"639605","DOI":"10.3389\/fimmu.2021.639605","article-title":"Cell-mediated immunological biomarkers and their diagnostic application in livestock and wildlife infected with Mycobacterium bovis","volume":"12","author":"Smith","year":"","journal-title":"Front. Immunol."},{"key":"ref76","doi-asserted-by":"publisher","first-page":"7074","DOI":"10.1038\/s41598-021-86398-6","article-title":"Temporal dynamics of intradermal cytokine response to tuberculin in Mycobacterium bovis BCG-vaccinated cattle using sampling microneedles","volume":"11","author":"Steinbach","year":"2021","journal-title":"Sci. Rep."},{"key":"ref77","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1016\/j.vetimm.2007.05.009","article-title":"Associations between cytokine gene expression and pathology in Mycobacterium bovis infected cattle","volume":"119","author":"Thacker","year":"2007","journal-title":"Vet. Immunol. Immunopathol."},{"key":"ref78","doi-asserted-by":"publisher","first-page":"1278","DOI":"10.1292\/jvms.21-0113","article-title":"Tuberculosis seroprevalence and comparison of hematology and biochemistry parameters between seropositive and seronegative captive Asian elephants of Nepal","volume":"83","author":"Thapa","year":"2021","journal-title":"J. Vet. Med. Sci."},{"key":"ref79","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1016\/j.anireprosci.2007.07.012","article-title":"Influence of oxidative stress and metabolic adaptation on PON1 activity and MDA level in transition dairy cows","volume":"108","author":"Turk","year":"2008","journal-title":"Anim. Reprod. Sci."},{"key":"ref80","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1007\/978-1-4939-0497-6_6","article-title":"Oxidative stress in tuberculosis","volume-title":"Studies on respiratory diseases","author":"Verma","year":"2014"},{"key":"ref81","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.cimid.2019.01.021","article-title":"Serum haptoglobin response in red deer naturally infected with tuberculosis","volume":"64","author":"Vicente","year":"2019","journal-title":"Comp. Immunol. Microbiol. Infect. Dis."},{"key":"ref82","doi-asserted-by":"publisher","first-page":"346","DOI":"10.1128\/CVI.05657-11","article-title":"Evaluation of gamma interferon (IFN-\u03b3)-induced protein 10 responses for detection of cattle infected with Mycobacterium bovis: comparisons to IFN-\u03b3 responses","volume":"19","author":"Waters","year":"2012","journal-title":"Clin. Vaccine Immunol."},{"key":"ref83","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1111\/j.1365-2249.2006.03053.x","article-title":"Cytokine expression profiles of bovine lymph nodes: effects of Mycobacterium bovis infection and bacille Calmette-Gu\u00e9rin vaccination","volume":"144","author":"Widdison","year":"2006","journal-title":"Clin. Exp. Immunol."},{"key":"ref84","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1054\/tube.2000.0272","article-title":"<article-title update=\"added\">BOVIGAMTM: an in vitro cellular diagnostic test for bovine tuberculosis","volume":"81","author":"Wood","year":"2001","journal-title":"Tuberculosis"},{"key":"ref85","doi-asserted-by":"publisher","first-page":"643","DOI":"10.21203\/rs.3.rs-1912881\/v1","article-title":"Evaluation of oxidative stress, compositional and biochemical changes in milk and serum of cows with subclinical mastitis","volume":"33","author":"Yehia","year":"2024","journal-title":"Comp. Clin. Pathol."}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2026.1765857\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T06:42:16Z","timestamp":1771569736000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2026.1765857\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,20]]},"references-count":85,"alternative-id":["10.3389\/fmicb.2026.1765857"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2026.1765857","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,20]]},"article-number":"1765857"}}