{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:27:30Z","timestamp":1787030850535,"version":"build-2736575974"},"reference-count":87,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2018,12,1]],"date-time":"2018-12-01T00:00:00Z","timestamp":1543622400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The outcome of intracellular parasitic infection can be determined by the immunoregulatory activities of natural regulatory CD4+ Foxp3+ T (Treg) cells and the anti-inflammatory cytokine IL-10. These mechanisms protect tissue but can also suppress antiparasitic CD4+ T cell responses. The specific contribution of these regulatory pathways during human parasitic diseases remains unclear. In this study, we investigated the roles of Treg cells and IL-10 during experimental visceral leishmaniasis caused by Leishmania donovani infection of C57BL\/6 mice. We report only a limited contribution of Treg cells in suppressing antiparasitic immunity, but important roles in delaying the development of splenic pathology and restricting leukocyte expansion. We next employed a range of cell-specific, IL-10\u2013 and IL-10R\u2013deficient mice and found these Treg cell functions were independent of IL-10. Instead, conventional CD4+ T cells and dendritic cells were the most important cellular sources of IL-10, and the absence of IL-10 in either cell population resulted in greater control of parasite growth but also caused accelerated breakdown in splenic microarchitecture. We also found that T cells, dendritic cells, and other myeloid cells were the main IL-10\u2013responding cells because in the absence of IL-10R expression by these cell populations, there was greater expansion of parasite-specific CD4+ T cell responses associated with improved control of parasite growth. Again, however, there was also an accelerated breakdown in splenic microarchitecture in these animals. Together, these findings identify distinct, cell-specific, immunoregulatory networks established during experimental visceral leishmaniasis that could be manipulated for clinical advantage.<\/jats:p>","DOI":"10.4049\/jimmunol.1701582","type":"journal-article","created":{"date-parts":[[2018,10,24]],"date-time":"2018-10-24T11:00:39Z","timestamp":1540378839000},"page":"3362-3372","source":"Crossref","is-referenced-by-count":43,"title":["Distinct Roles for CD4+ Foxp3+ Regulatory T Cells and IL-10\u2013Mediated Immunoregulatory Mechanisms during Experimental Visceral Leishmaniasis Caused by\n                    <i>Leishmania donovani<\/i>"],"prefix":"10.1093","volume":"201","author":[{"given":"Patrick T","family":"Bunn","sequence":"first","affiliation":[{"name":"QIMR Berghofer Medical Research Institute , Brisbane, Queensland 4006 ,","place":["Australia"]},{"name":"Institute of Glycomics, Griffith University , Gold Coast, Queensland 4215 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcela","family":"Montes de Oca","sequence":"additional","affiliation":[{"name":"QIMR Berghofer Medical Research Institute , Brisbane, Queensland 4006 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabian","family":"de Labastida Rivera","sequence":"additional","affiliation":[{"name":"QIMR Berghofer Medical Research Institute , Brisbane, Queensland 4006 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajiv","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Banaras Hindu University , Varanasi 221005 ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanna S","family":"Ng","sequence":"additional","affiliation":[{"name":"School of Natural Sciences, Griffith University , Nathan, Queensland 4111 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5881-263X","authenticated-orcid":false,"given":"Chelsea L","family":"Edwards","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Queensland , Brisbane, Queensland 4006 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca J","family":"Faleiro","sequence":"additional","affiliation":[{"name":"QIMR Berghofer Medical Research Institute , Brisbane, Queensland 4006 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5453-070X","authenticated-orcid":false,"given":"Meru","family":"Sheel","sequence":"additional","affiliation":[{"name":"QIMR Berghofer Medical Research Institute , Brisbane, Queensland 4006 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiona 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Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2260-0026","authenticated-orcid":false,"given":"Ashraful","family":"Haque","sequence":"additional","affiliation":[{"name":"QIMR Berghofer Medical Research Institute , Brisbane, Queensland 4006 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jude E","family":"Uzonna","sequence":"additional","affiliation":[{"name":"Department of Immunology, College of Medicine, University of Manitoba , Winnipeg, Manitoba R3E 0T5 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geoffrey R","family":"Hill","sequence":"additional","affiliation":[{"name":"QIMR Berghofer Medical Research Institute , Brisbane, Queensland 4006 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2813-4804","authenticated-orcid":false,"given":"Christian 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