{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T14:13:09Z","timestamp":1789913589560,"version":"4.0.1"},"reference-count":24,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2017,11,20]],"date-time":"2017-11-20T00:00:00Z","timestamp":1511136000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Department of Biotechnology, Government of India","award":["DBT\/PR14092\/MED\/29\/190\/2010"],"award-info":[{"award-number":["DBT\/PR14092\/MED\/29\/190\/2010"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,2,7]]},"abstract":"<jats:title>Summary<\/jats:title>\n               <jats:p>Visceral leishmaniasis (VL) is a disseminated and lethal disease of reticulo-endothelial system caused by protozoan parasites Leishmania donovani and L. infantum, which are known to induce host T cell suppression. To understand the impact of parasite load on T cell function, the present was focused on parasite load with T cell function in bone marrow of 26 VL patients. We observed significant enrichment of forkhead box protein 3 (FoxP3)+ (P = 0\u00b70003) and interleukin (IL)-10+ FoxP3+ regulatory T cells (Treg) (P = 0\u00b7004) in the bone marrow (BM) of patients with high parasite load (HPL) compared with low parasite load (LPL). Concordantly, T effector cells producing interferon (IFN)-\u03b3 (P = 0\u00b7005) and IL-17A (P = 0\u00b7002) were reduced in the BM of HPL. Blocking of Treg-cell derived suppressive cytokines [(IL-10 and transforming growth factor (TGF)-\u03b2] rescued the effector T cells and their functions. However, it was observed that TGF-\u03b2 levels were dominant, favouring Treg cell differentiation. Furthermore, the low ratio of IL-6\/TGF-\u03b2 favours the suppressive milieu in HPL patients. Here we show the change in levels of various cytokines with the parasitic load during active VL, which could be helpful in devising newer immunotherapeutic strategies against this disease.<\/jats:p>","DOI":"10.1111\/cei.13074","type":"journal-article","created":{"date-parts":[[2017,10,23]],"date-time":"2017-10-23T10:36:38Z","timestamp":1508754998000},"page":"318-327","source":"Crossref","is-referenced-by-count":11,"title":["T cell suppression in the bone marrow of visceral leishmaniasis patients: impact of parasite load"],"prefix":"10.1093","volume":"191","author":[{"given":"P","family":"Kumar","sequence":"first","affiliation":[{"name":"Department of T.I.I., All India Institute of Medical Sciences (AIIMS), Ansari Nagar, New Delhi, India"},{"name":"Amity Institute of Virology and Immunology, Amity University, Noida, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P","family":"Misra","sequence":"additional","affiliation":[{"name":"Department of T.I.I., All India Institute of Medical Sciences (AIIMS), Ansari Nagar, New Delhi, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C P","family":"Thakur","sequence":"additional","affiliation":[{"name":"Balaji Utthan Sansthan, Patna, Bihar, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Saurabh","sequence":"additional","affiliation":[{"name":"Department of T.I.I., All India Institute of Medical Sciences (AIIMS), Ansari Nagar, New Delhi, India"},{"name":"Amity Institute of Virology and Immunology, Amity University, Noida, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N","family":"Rishi","sequence":"additional","affiliation":[{"name":"Amity Institute of Virology and Immunology, Amity University, Noida, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0572-7885","authenticated-orcid":false,"given":"D K","family":"Mitra","sequence":"additional","affiliation":[{"name":"Department of T.I.I., All India Institute of Medical Sciences (AIIMS), Ansari Nagar, New Delhi, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2017,11,20]]},"reference":[{"key":"2021120808195951700_cei13074-bib-0001","doi-asserted-by":"crossref","first-page":"e0004349","DOI":"10.1371\/journal.pntd.0004349","article-title":"A historical overview of the classification, evolution, and dispersion of leishmania parasites and sandflies","volume":"10","author":"Akhoundi","year":"2016","journal-title":"PLOS Negl Trop Dis"},{"key":"2021120808195951700_cei13074-bib-0002","doi-asserted-by":"crossref","first-page":"153","DOI":"10.3389\/fimmu.2016.00153","article-title":"The contribution of immune evasive mechanisms to parasite persistence in visceral leishmaniasis","volume":"7","author":"de Freitas","year":"2016","journal-title":"Front Immunol"},{"key":"2021120808195951700_cei13074-bib-0003","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1186\/s13071-016-1412-x","article-title":"Regulation of immunity during visceral Leishmania infection","volume":"9","author":"Rodrigues","year":"2016","journal-title":"Parasit Vectors"},{"key":"2021120808195951700_cei13074-bib-0004","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.trstmh.2010.09.006","article-title":"Diagnosis of visceral leishmaniasis","volume":"105","author":"Srivastava","year":"2011","journal-title":"Trans R Soc Trop Med Hyg"},{"key":"2021120808195951700_cei13074-bib-0005","first-page":"182","article-title":"Bone marrow negative visceral leishmaniasis in an adolescent male","volume":"8","author":"Jetley","year":"2013","journal-title":"Iran J Parasitol"},{"key":"2021120808195951700_cei13074-bib-0006","doi-asserted-by":"crossref","first-page":"3147","DOI":"10.1128\/JCM.00372-14","article-title":"Molecular tools for diagnosis of visceral leishmaniasis: systematic review and meta-analysis of diagnostic test accuracy","volume":"52","author":"de Ruiter","year":"2014","journal-title":"J Clin Microbiol"},{"key":"2021120808195951700_cei13074-bib-0007","first-page":"01","article-title":"Control of the Leishmaniases: report of a meeting of the WHO Expert Committee on the Control of Leishmaniases, Geneva, 22\u201326 March 2010","volume":"2010","author":"World Health Organization (WHO)","year":"2010","journal-title":"Tech Rep Ser"},{"key":"2021120808195951700_cei13074-bib-0008","doi-asserted-by":"crossref","first-page":"189","DOI":"10.3347\/kjp.2014.52.2.189","article-title":"Visceral leishmaniasis without fever in an 11-month-old infant: a rare clinical feature of Kala-azar","volume":"52","author":"Sayyahfar","year":"2014","journal-title":"Korean J Parasitol"},{"key":"2021120808195951700_cei13074-bib-0009","first-page":"1","article-title":"Arginase activity in the blood of patients with visceral leishmaniasis and HIV infection","volume":"7","author":"Yegnasew Takele","year":"2012","journal-title":"PLOS Negl Trop Dis"},{"key":"2021120808195951700_cei13074-bib-0010","first-page":"1","article-title":"Simultaneous occurrence of ocular, disseminated mucocutaneous, and multivisceral involvement of leishmaniasis","volume":"2014","author":"Philips","year":"2014","journal-title":"Case Rep Infect Dis"},{"key":"2021120808195951700_cei13074-bib-0011","doi-asserted-by":"crossref","first-page":"135","DOI":"10.4103\/0974-777X.62876","article-title":"Immunological perspectives of leishmaniasis","volume":"2","author":"Nyl\u00e9n","year":"2010","journal-title":"J Glob Infect Dis"},{"key":"2021120808195951700_cei13074-bib-0012","doi-asserted-by":"crossref","first-page":"99","DOI":"10.3389\/fimmu.2012.00099","article-title":"Vaccine development against leishmania donovani","volume":"3","author":"Das","year":"2012","journal-title":"Front Immunol"},{"key":"2021120808195951700_cei13074-bib-0013","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1155\/2013\/275253","article-title":"Post-Kala-Azar dermal leishmaniasis: a paradigm of paradoxical immune reconstitution syndrome in non-HIV\/AIDS patients","volume":"2013","author":"Khalil","year":"2013","journal-title":"J Trop Med"},{"key":"2021120808195951700_cei13074-bib-0014","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.pone.0031551","article-title":"Regulatory T cells suppress T cell activation at the pathologic site of human visceral leishmaniasis","volume":"7","author":"Rai","year":"2012","journal-title":"PLOS ONE"},{"key":"2021120808195951700_cei13074-bib-0015","first-page":"2379","article-title":"IL-17 and IL-22 are associated with protection against human kala azar caused by Leishmania donovani","volume":"119","author":"Pitta","year":"2009","journal-title":"J Clin Invest"},{"key":"2021120808195951700_cei13074-bib-0016","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.pone.0044728","article-title":"Foxp3+ regulatory T cells among tuberculosis patients: impact on prognosis and restoration of antigen specific IFN-gamma producing T cells","volume":"7","author":"Singh","year":"2012","journal-title":"PLOS ONE"},{"key":"2021120808195951700_cei13074-bib-0017","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1164\/rccm.200804-529OC","article-title":"FoxP3+ regulatory T cells suppress effector T-cell function at pathologic site in miliary tuberculosis","volume":"179","author":"Sharma","year":"2009","journal-title":"Am J Respir Crit Care Med"},{"key":"2021120808195951700_cei13074-bib-0018","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/j.coph.2009.04.008","article-title":"Anti-inflammatory and pro-inflammatory roles of TGF-beta, IL-10, and IL-22 in immunity and autoimmunity","volume":"9","author":"Sanjabi","year":"2009","journal-title":"Curr Opin Pharmacol"},{"key":"2021120808195951700_cei13074-bib-0019","doi-asserted-by":"crossref","first-page":"1830","DOI":"10.1002\/eji.201040391","article-title":"IL-6: regulator of Treg\/Th17 balance","volume":"40","author":"Kimura","year":"2010","journal-title":"Eur J Immunol"},{"key":"2021120808195951700_cei13074-bib-0020","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1128\/JCM.05067-11","article-title":"Peripheral blood buffy coat smear: a promising tool for diagnosis of visceral leishmaniasis","volume":"50","author":"Salam","year":"2012","journal-title":"J Clin Microbiol"},{"key":"2021120808195951700_cei13074-bib-0021","doi-asserted-by":"crossref","first-page":"e0004422","DOI":"10.1371\/journal.pntd.0004422","article-title":"Induction of IL-10 and TGFbeta from CD4+CD25+FoxP3+ T cells correlates with parasite load in Indian Kala-azar patients infected with Leishmania donovani","volume":"10","author":"Bhattacharya","year":"2016","journal-title":"PLOS Negl Trop Dis"},{"key":"2021120808195951700_cei13074-bib-0022","doi-asserted-by":"crossref","first-page":"2613","DOI":"10.4049\/jimmunol.170.5.2613","article-title":"Activation of TGF- by Leishmania chagasi: importance for parasite survival in macrophages","volume":"170","author":"Gantt","year":"2003","journal-title":"J Immunol"},{"key":"2021120808195951700_cei13074-bib-0023","doi-asserted-by":"crossref","first-page":"251","DOI":"10.3389\/fimmu.2012.00251","article-title":"Immunobiology of visceral leishmaniasis","volume":"3","author":"Kumar","year":"2012","journal-title":"Front Immunol"},{"key":"2021120808195951700_cei13074-bib-0024","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1590\/0074-02760160529","article-title":"Protection mediated by chemokine CXCL10 in BALB\/c mice infected by Leishmania infantum","volume":"112","author":"Figueiredo","year":"2017","journal-title":"Mem Inst Oswaldo Cruz"}],"container-title":["Clinical and Experimental Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcei.13074","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/cei\/article-pdf\/191\/3\/318\/41644588\/cei13074.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cei\/article-pdf\/191\/3\/318\/41644588\/cei13074.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T16:25:45Z","timestamp":1641054345000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/cei\/article\/191\/3\/318\/6412309"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,11,20]]},"references-count":24,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2017,11,20]]},"published-print":{"date-parts":[[2018,2,7]]}},"URL":"https:\/\/doi.org\/10.1111\/cei.13074","relation":{},"ISSN":["0009-9104","1365-2249"],"issn-type":[{"value":"0009-9104","type":"print"},{"value":"1365-2249","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2018,3]]},"published":{"date-parts":[[2017,11,20]]}}}