{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T13:20:54Z","timestamp":1761312054570,"version":"build-2065373602"},"reference-count":35,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2024,6,4]],"date-time":"2024-06-04T00:00:00Z","timestamp":1717459200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001503","name":"National Agricultural Science Funds (NASF)","doi-asserted-by":"publisher","award":["NASF\/ABS-9009\/2022-23","TAR\/2022\/000627"],"award-info":[{"award-number":["NASF\/ABS-9009\/2022-23","TAR\/2022\/000627"]}],"id":[{"id":"10.13039\/501100001503","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001843","name":"DST SERB-TARE","doi-asserted-by":"publisher","award":["NASF\/ABS-9009\/2022-23","TAR\/2022\/000627"],"award-info":[{"award-number":["NASF\/ABS-9009\/2022-23","TAR\/2022\/000627"]}],"id":[{"id":"10.13039\/501100001843","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Mycobacterium avium subspecies paratuberculosis (MAP) infection leads to chronic, persistent granulomatous enteritis, causing prolonged diarrhoea and emaciation. The disease is managed using medications such as antibiotics, live vaccines, mycobacteriophage therapies and other treatments; however, a notable proportion of affected animals do not show improvement with this approach. We hypothesise that immunoinhibitory receptors TIM-3 (T cell immunoglobulin mucin protein-3) and PD-1 (Programmed death receptor 1) may be upregulated on Peripheral blood mononuclear cells (PBMCs) of MAP-seropositive bovines, potentially contributing to immune exhaustion. Samples (blood and faeces) were collected from 32 diarrhoeic bovines suspected of MAP infection; eight apparently healthy buffaloes from the dairy farm at Hisar, Haryana and from 14 cows (suffering from chronic diarrhoea, weakness and emaciation) housed in stray cattle shed. MAP infection was estimated using indigenous ELISA (i-ELISA), faecal IS900 PCR, culture and acid-fast staining. TIM-3 and PD-1 gene expression on PBMCs were determined using qRT-PCR. TIM3 expression was relatively higher (~400-fold, 330-fold, 112-fold, 65-fold and 16-fold) in 5 chronically diarrhoeic PBMCs samples (MAP-seropositive), and higher PD-1 expression (around ~7-fold, 1.75-fold, 2.5-fold, 7.6-fold) was recorded in 4 diarrhoeic MAP-seropositive animals, compared to apparently healthy and other MAP-seronegative diarrhoeic animals. High co-expression of TIM-3 and PD-1 levels was also recorded in chronically diarrhoeic, emaciated stray cattle. Understanding immune responses in field conditions might aid in the therapeutic management of paratuberculosis.<\/jats:p>","DOI":"10.3390\/pathogens13060473","type":"journal-article","created":{"date-parts":[[2024,6,4]],"date-time":"2024-06-04T11:48:50Z","timestamp":1717501730000},"page":"473","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Evaluation of Immune Exhaustion and Co-Inhibitory Receptor Expression in Mycobacterium avium Subspecies paratuberculosis (MAP) Seropositive Diarrhoeic Bovines"],"prefix":"10.3390","volume":"13","author":[{"given":"Shalini","family":"Sharma","sequence":"first","affiliation":[{"name":"Department of Veterinary Physiology and Biochemistry, Lala Lajpat Rai University of Veterinary and Animal Sciences, Hisar 125004, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Khushbu","family":"Sharma","sequence":"additional","affiliation":[{"name":"Department of Veterinary Physiology and Biochemistry, Lala Lajpat Rai University of Veterinary and Animal Sciences, Hisar 125004, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ram","family":"Kumar","sequence":"additional","affiliation":[{"name":"National Centre for Veterinary Type Cultures, ICAR-NRC on Equines Sirsa Road, Hisar 125001, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deen","family":"Dayal","sequence":"additional","affiliation":[{"name":"Department of Bio-Technology, GLA University, Post-Chaumuhan, Mathura 281406, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shweta","family":"Dhanda","sequence":"additional","affiliation":[{"name":"National Centre for Veterinary Type Cultures, ICAR-NRC on Equines Sirsa Road, Hisar 125001, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3974-9409","authenticated-orcid":false,"given":"Naveen","family":"Kumar","sequence":"additional","affiliation":[{"name":"National Centre for Veterinary Type Cultures, ICAR-NRC on Equines Sirsa Road, Hisar 125001, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5940-4638","authenticated-orcid":false,"given":"Kundan Kumar","family":"Chaubey","sequence":"additional","affiliation":[{"name":"School of Basic and Applied Sciences, Sanskriti University, Mathura 281401, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shoor Vir","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Bio-Technology, GLA University, Post-Chaumuhan, Mathura 281406, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-7270-6629","authenticated-orcid":false,"given":"Sikander","family":"Banger","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, Lala Lajpat Rai University of Veterinary and Animal Sciences, Hisar 125004, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8800-3681","authenticated-orcid":false,"given":"Vishal","family":"Sharma","sequence":"additional","affiliation":[{"name":"Department of Livestock Production Management, Lala Lajpat Rai University of Veterinary and Animal Sciences, Hisar 125004, India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,4]]},"reference":[{"key":"ref_1","unstructured":"Brouwers, T. 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