{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T18:47:15Z","timestamp":1787078835594,"version":"build-2736575974"},"update-to":[{"DOI":"10.1371\/journal.pntd.0011960","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,3,7]],"date-time":"2024-03-07T00:00:00Z","timestamp":1709769600000}}],"reference-count":42,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2024,2,26]],"date-time":"2024-02-26T00:00:00Z","timestamp":1708905600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["(grant no. 2U19AI074321)"],"award-info":[{"award-number":["(grant no. 2U19AI074321)"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001411","name":"Indian Council of Medical Research","doi-asserted-by":"publisher","award":["2020-9898"],"award-info":[{"award-number":["2020-9898"]}],"id":[{"id":"10.13039\/501100001411","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001411","name":"Indian Council of Medical Research","doi-asserted-by":"publisher","award":["2020-9898"],"award-info":[{"award-number":["2020-9898"]}],"id":[{"id":"10.13039\/501100001411","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002742","name":"Banaras Hindu University","doi-asserted-by":"publisher","award":["Institute of Eminence (IoE) Incentive Grant"],"award-info":[{"award-number":["Institute of Eminence (IoE) Incentive Grant"]}],"id":[{"id":"10.13039\/501100002742","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002742","name":"Banaras Hindu University","doi-asserted-by":"publisher","award":["Institute of Eminence (IoE) Seed Grant"],"award-info":[{"award-number":["Institute of Eminence (IoE) Seed Grant"]}],"id":[{"id":"10.13039\/501100002742","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"\n Background<\/jats:title>\n \n CD4\n +<\/jats:sup>\n T cells play a central role in control of\n L<\/jats:italic>\n .\n donovani<\/jats:italic>\n infection, through IFN-\u03b3 production required for activation of macrophages and killing of intracellular parasites. Impaired control of parasites can in part be explained by hampered CD4\n +<\/jats:sup>\n T cells effector functions in visceral leishmaniasis (VL) patients. In a recent studies that defined transcriptional signatures for CD4\n +<\/jats:sup>\n T cells from active VL patients, we found that expression of the IL-7 receptor alpha chain (IL-7R\n \u03b1<\/jats:sc>\n ; CD127) was downregulated, compared to CD4\n +<\/jats:sup>\n T cells from endemic controls (ECs). Since IL-7 signaling is critical for the survival and homeostatic maintenance of CD4\n +<\/jats:sup>\n T cells, we investigated this signaling pathway in VL patients, relative to ECs.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n CD4\n +<\/jats:sup>\n T cells were enriched from peripheral blood collected from VL patients and EC subjects and expression of\n IL7<\/jats:italic>\n and\n IL7RA<\/jats:italic>\n mRNA was measured by real time qPCR. IL-7 signaling potential and surface expression of CD127 and CD132 on CD4\n +<\/jats:sup>\n T cell was analyzed by multicolor flow cytometry. Plasma levels of soluble IL-7 and sIL-7R\u03b1 were measured by ELISA.\n <\/jats:p>\n <\/jats:sec>\n \n Result<\/jats:title>\n \n Transcriptional profiling data sets generated previously from our group showed lower\n IL7RA<\/jats:italic>\n mRNA expression in VL CD4\n +<\/jats:sup>\n T cells as compared to EC. A significant reduction was, however not seen when assessing\n IL7RA<\/jats:italic>\n mRNA by RT-qPCR. Yet, the levels of soluble IL-7R\u03b1 (sIL-7R\u03b1) were reduced in plasma of VL patients compared to ECs. Furthermore, the levels of soluble IL-7 were higher in plasma from VL patients compared to ECs. Interestingly, expression of the IL-7R\u03b1 protein was higher on VL patient CD4\n +<\/jats:sup>\n T cells as compared to EC, with activated CD38\n +<\/jats:sup>\n CD4\n +<\/jats:sup>\n T cells showing higher surface expression of IL-7R\u03b1 compared to CD38\n -<\/jats:sup>\n CD4\n +<\/jats:sup>\n T cells in VL patients. CD4\n +<\/jats:sup>\n T cells from VL patients had higher signaling potential baseline and after stimulation with recombinant human IL-7 (rhIL-7) compared to EC, as measured by phosphorylation of STAT5 (pSTAT5). Interestingly, it was the CD38 negative cells that had the highest level of pSTAT5 in VL patient CD4\n +<\/jats:sup>\n T cells after IL-7 stimulation. Thus, despite unaltered or potentially lowered\n IL7RA<\/jats:italic>\n mRNA expression by CD4\n +<\/jats:sup>\n T cells from VL patients, the surface expression of the IL-7R\u03b1 was higher compared to EC and increased pSTAT5 was seen following exposure to rhIL-7. Accordingly, IL-7 signaling appears to be functional and even enhanced in VL CD4\n +<\/jats:sup>\n T cells and cannot explain the impaired effector function of VL CD4\n +<\/jats:sup>\n T cells. The enhanced plasma IL-7 may serve as part of homeostatic feedback mechanism regulating\n IL7RA<\/jats:italic>\n expression in CD4\n +<\/jats:sup>\n T cells.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1371\/journal.pntd.0011960","type":"journal-article","created":{"date-parts":[[2024,2,26]],"date-time":"2024-02-26T13:39:53Z","timestamp":1708954793000},"page":"e0011960","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["Altered IL-7 signaling in CD4+ T cells from patients with visceral leishmaniasis"],"prefix":"10.1371","volume":"18","author":[{"given":"Shashi","family":"Kumar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shashi Bhushan","family":"Chauhan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shreya","family":"Upadhyay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siddharth Sankar","family":"Singh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vimal","family":"Verma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajiv","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Engwerda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Nyl\u00e9n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9988-582X","authenticated-orcid":true,"given":"Shyam","family":"Sundar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,2,26]]},"reference":[{"key":"pntd.0011960.ref001","unstructured":"Leishmaniasis. 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