{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T08:00:55Z","timestamp":1772006455415,"version":"3.50.1"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T00:00:00Z","timestamp":1771977600000},"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. Immunol."],"abstract":"<jats:p>\n                    <jats:italic>Mycobacterium bovis<\/jats:italic>\n                    (\n                    <jats:italic>M. bovis<\/jats:italic>\n                    ) is the primary agent of Bovine tuberculosis (bTB) in cattle. It represents both a threat to human health and the cattle industry worldwide. Improving bTB diagnostic performance in cattle represents a key step in eradicating the disease. The interferon-gamma (IFN-\u03b3) release (IGRA) blood assay is routinely used in the diagnosis of\n                    <jats:italic>M. bovis<\/jats:italic>\n                    infection, but additional cytokines might be useful as biomarkers of this infection in cattle. In our study, we evaluated the utility of sixteen immune cytokines as diagnostic biomarkers of\n                    <jats:italic>M. bovis<\/jats:italic>\n                    infection. Fifty-five cattle were used in this study: healthy animals (N = 19), infected (IFN-\u03b3 test positive, no post-mortem lesions; N = 17), and affected (IFN-\u03b3 test positive, visible post-mortem lesions; N = 19). Heparin blood samples were stimulated\n                    <jats:italic>in vitro<\/jats:italic>\n                    with bovine purified protein derivative (PPD-B), alongside controls. After 18\u201324 h of incubation, plasma were collected and levels of 16 key cytokines were measured: IL-1\u03b1, IL-4, IL-6, IL-10, IL-17, IL-36Ra, MIP-1\u03b1, IP-10, MCP-1, TNF, VEGF-A, IFN-\u03b3, IL-23, IL-27, IL-35, and THBS-1. We observed that both\n                    <jats:italic>M. bovis<\/jats:italic>\n                    exposed cattle (both infected and affected) released higher levels of PPD-B specific IFN-\u03b3 and IP-10. On the contrary, only cattle belonging to the affected group released higher levels of PPD-B specific IL-4, IL-17, and TNF compared to healthy subjects. Canonical discriminant analyses (CDA) indicated that IP-10, IL-4, IL-17, and TNF could be useful biomarkers for infection status. In particular, our data suggest that the parallel measurement of IFN-\u03b3 and IP-10 might improve the diagnosis of\n                    <jats:italic>M. bovis<\/jats:italic>\n                    infection in cattle in terms of sensitivity and specificity, although this should be validated on a larger set of animals. In the CDA analysis, only a modest separation between infected and affected cattle was observed. Nevertheless, our data suggested that IL-4, IL-10, and TNF might improve, at least in part, the differentiation of cattle in diverse stages of TB infection. Overall, the data generated in our study provide a foundation to improve the diagnosis and staging of\n                    <jats:italic>M. bovis<\/jats:italic>\n                    in cattle.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1786944","type":"journal-article","created":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T07:04:40Z","timestamp":1772003080000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploring alternative cytokines as potential biomarkers for Mycobacterium bovis infection in cattle"],"prefix":"10.3389","volume":"17","author":[{"given":"Giulia","family":"Franzoni","sequence":"first","affiliation":[{"name":"Department of Animal Health, Istituto Zooprofilattico Sperimentale della Sardegna","place":["Sassari, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Federica","family":"Signorelli","sequence":"additional","affiliation":[{"name":"Council for Agricultural Research and Economics (CREA) - 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