{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T17:33:43Z","timestamp":1775583223887,"version":"3.50.1"},"reference-count":70,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2024,12,12]],"date-time":"2024-12-12T00:00:00Z","timestamp":1733961600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001602","name":"Science Foundation Ireland","doi-asserted-by":"publisher","award":["17\/CDA\/4717"],"award-info":[{"award-number":["17\/CDA\/4717"]}],"id":[{"id":"10.13039\/501100001602","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001592","name":"Higher Education Authority","doi-asserted-by":"publisher","award":["Vit-TB"],"award-info":[{"award-number":["Vit-TB"]}],"id":[{"id":"10.13039\/501100001592","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p><jats:italic>Mycobacterium bovis<\/jats:italic> (<jats:italic>M<\/jats:italic>. <jats:italic>bovis<\/jats:italic>) causes bovine tuberculosis (bTB). The challenges in controlling and eradicating this zoonotic disease are compounded by our incomplete understanding of the host immune response. In this study, we used high-throughput bulk RNA sequencing (RNA-seq) to characterise the response profiles of \u03b3\u03b4 T cells to antigenic stimulation using purified protein derivate from <jats:italic>M<\/jats:italic>. <jats:italic>bovis<\/jats:italic> (PPDb). \u03b3\u03b4 T cells are a subgroup of T cells that bridge innate and adaptive immunity and have known anti-mycobacterial response mechanisms. These cells are usually classified based on the expression of a pathogen-recognition receptor, Workshop Cluster 1 (WC1), into two main subsets: WC1.1<jats:sup>+<\/jats:sup> and WC1.2<jats:sup>+<\/jats:sup>. Previous studies have identified a preferential transcriptomic response in WC1.1<jats:sup>+<\/jats:sup> cells during natural bTB infection, suggesting a subset-specific response to mycobacterial antigens. This follow on study tested the hypothesis that a subset specific response would also be apparent from \u03b3\u03b4 T cells from infected cattle after repeat stimulation. Peripheral blood was collected from Holstein-Friesian cattle naturally infected with <jats:italic>M<\/jats:italic>. <jats:italic>bovis<\/jats:italic>, confirmed by a single intradermal comparative tuberculin test (SICTT) and IFN-\u03b3 ELISA and stimulated with 10 \u03bcg\/ml PPDb for 6 hours. After whole blood stimulation, WC1.1<jats:sup>+<\/jats:sup> and WC1.2<jats:sup>+<\/jats:sup> \u03b3\u03b4 T cell subsets were isolated using magnetic cell sorting (n = 5 per group). High-quality RNA was extracted from each purified lymphocyte subset (WC1.1<jats:sup>+<\/jats:sup> and WC1.2<jats:sup>+<\/jats:sup>) to generate transcriptomes using bulk RNA sequencing, resulting in 20 RNA-seq libraries. Transcriptomic analysis revealed 111 differentially expressed genes (DEGs) common to both WC1.1<jats:sup>+<\/jats:sup> and WC1.2<jats:sup>+<\/jats:sup> \u03b3\u03b4 T cell compartments, including upregulation of <jats:italic>IL1A<\/jats:italic>, <jats:italic>IL1B<\/jats:italic>, <jats:italic>IL6<\/jats:italic>, <jats:italic>IL17A<\/jats:italic>, <jats:italic>IL17F<\/jats:italic>, and <jats:italic>IFNG<\/jats:italic> genes (FDR-<jats:italic>P<\/jats:italic><jats:sub>adj.<\/jats:sub> &lt; 0.1). Interestingly, the WC1.2<jats:sup>+<\/jats:sup> cells showed upregulation of <jats:italic>IL10<\/jats:italic>, <jats:italic>CCL22<\/jats:italic>, and <jats:italic>GZMA<\/jats:italic> (log<jats:sub>2<\/jats:sub>FC \u2265 1.5, and FDR-<jats:italic>P<\/jats:italic><jats:sub>adj.<\/jats:sub> &lt; 0.1). In conclusion, while WC1.1<jats:sup>+<\/jats:sup> and WC1.2<jats:sup>+<\/jats:sup> \u03b3\u03b4 T cells exhibit a conserved inflammatory response to PPDb, differences in anti-inflammatory and antimicrobial gene expression between these cell subsets provide new insights into their effector functions in response to mycobacterial antigens.<\/jats:p>","DOI":"10.1371\/journal.pone.0311854","type":"journal-article","created":{"date-parts":[[2024,12,12]],"date-time":"2024-12-12T18:31:12Z","timestamp":1734028272000},"page":"e0311854","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Comparative analysis of WC1.1+ and WC1.2+ \u03b3\u03b4 T cell subset responses from cattle naturally infected with Mycobacterium bovis to repeat stimulation with mycobacterial antigens"],"prefix":"10.1371","volume":"19","author":[{"given":"Alia","family":"Parveen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sajad A.","family":"Bhat","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mahmoud","family":"Elnaggar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3051-8586","authenticated-orcid":true,"given":"Kieran G.","family":"Meade","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2024,12,12]]},"reference":[{"issue":"3","key":"pone.0311854.ref001","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1128\/CMR.14.3.489-512.2001","article-title":"Mycobacterium avium subsp. paratuberculosis in Veterinary Medicine.","volume":"14","author":"NB 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