{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T01:34:25Z","timestamp":1792892065080,"version":"4.5.0"},"reference-count":55,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2019,12,10]],"date-time":"2019-12-10T00:00:00Z","timestamp":1575936000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010757","name":"National Centre for the Replacement Refinement and Reduction of Animals in Research","doi-asserted-by":"publisher","award":["NC.CO13117"],"award-info":[{"award-number":["NC.CO13117"]}],"id":[{"id":"10.13039\/501100010757","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010757","name":"National Centre for the Replacement Refinement and Reduction of Animals in Research","doi-asserted-by":"publisher","award":["NC\/CO13295"],"award-info":[{"award-number":["NC\/CO13295"]}],"id":[{"id":"10.13039\/501100010757","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006041","name":"Innovate UK","doi-asserted-by":"publisher","award":["NC.CO13117"],"award-info":[{"award-number":["NC.CO13117"]}],"id":[{"id":"10.13039\/501100006041","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006041","name":"Innovate UK","doi-asserted-by":"publisher","award":["NC\/CO13295"],"award-info":[{"award-number":["NC\/CO13295"]}],"id":[{"id":"10.13039\/501100006041","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Medical Research Council","award":["G1000230 , MR\/J008702\/1"],"award-info":[{"award-number":["G1000230 , MR\/J008702\/1"]}]},{"name":"Wellcome Trust","award":["WT104726"],"award-info":[{"award-number":["WT104726"]}]}],"content-domain":{"domain":["wellcomeopenresearch.org"],"crossmark-restriction":false},"short-container-title":["Wellcome Open Res"],"abstract":"<ns4:p>\n                    <ns4:bold>Background:<\/ns4:bold>\n                    Liposomal amphotericin B (AmBisome\u00ae) as a treatment modality for visceral leishmaniasis (VL) has had significant impact on patient care in some but not all regions where VL is endemic.\u00a0 As the mode of action of AmBisome\u00ae\n                    <ns4:italic>in vivo<\/ns4:italic>\n                    is poorly understood, we compared the tissue-specific transcriptome in drug-treated vs untreated mice with experimental VL.\u00a0 \u00a0\n                  <\/ns4:p>\n                  <ns4:p>\n                    <ns4:bold>Methods:\u00a0<\/ns4:bold>\n                    BALB\/c mice infected with\n                    <ns4:italic>L. donovani w<\/ns4:italic>\n                    ere treated with 8mg\/kg AmBisome\u00ae, resulting in parasite elimination from liver and spleen over a 7-day period. At day 1 and day 7 post treatment (R\n                    <ns4:sub>x<\/ns4:sub>\n                    +1 and R\n                    <ns4:sub>x<\/ns4:sub>\n                    +7), transcriptomic profiling was performed on spleen and liver tissue from treated and untreated mice and uninfected mice.\u00a0 BALB\/c mice infected with\n                    <ns4:italic>M. bovis<\/ns4:italic>\n                    BCG (an organism resistant to amphotericin B) were analysed to distinguish between direct effects of AmBisome\u00ae and those secondary to parasite death. \u00a0\n                  <\/ns4:p>\n                  <ns4:p>\n                    <ns4:bold>Results:<\/ns4:bold>\n                    AmBisome\u00ae treatment lead to rapid parasitological clearance.\u00a0 At R\n                    <ns4:sub>x<\/ns4:sub>\n                    +1, spleen and liver displayed only 46 and 88 differentially expressed (DE) genes (P&lt;0.05; 2-fold change) respectively. In liver, significant enrichment was seen for pathways associated with TNF, fatty acids and sterol biosynthesis.\u00a0 At R\n                    <ns4:sub>x<\/ns4:sub>\n                    +7, the number of DE genes was increased (spleen, 113; liver 400).\u00a0 In spleen, these included many immune related genes known to be involved in anti-leishmanial immunity. In liver, changes in transcriptome were largely accounted for by loss of granulomas.\u00a0\u00a0 PCA analysis indicated that treatment only partially restored homeostasis.\u00a0 Analysis of BCG-infected mice treated with AmBisome\u00ae revealed a pattern of immune modulation mainly targeting macrophage function. \u00a0\n                  <\/ns4:p>\n                  <ns4:p>\n                    <ns4:bold>Conclusions:<\/ns4:bold>\n                    Our data indicate that the tissue response to AmBisome\u00ae treatment varies between target organs and that full restoration of homeostasis is not achieved at parasitological cure.\u00a0 The pathways required to restore homeostasis deserve fuller attention, to understand mechanisms associated with treatment failure and relapse and to promote more rapid restoration of immune competence.\n                  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status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.21956\/wellcomeopenres.17094.r37347, Yasuyuki Goto, Laboratory of Molecular Immunology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan, 27 Dec 2019, version 1, indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/4-198\/v1#referee-response-37347","order":0,"name":"referee-response-37347","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.21956\/wellcomeopenres.17094.r37344, Syamal Roy, National Institute of Pharmaceutical Education & Research, Kolkata, India, 14 Jan 2020, version 1, indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/4-198\/v1#referee-response-37344","order":1,"name":"referee-response-37344","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"This work was funded by a National Centre for Replacement, Refinement and Reduction of Animal in Research (NC3Rs) \/ Innovate UK CRACKIT Challenge Award (NC.CO13117 and NC\/CO13295 to PMK, SLC, JT and JM), by a UK MRC Programme Grant (G1000230 to PMK) and by a Wellcome Trust Senior Investigator Award (WT104726 to PMK). KS and SLC were also supported by UK MRC (MR\/J008702\/1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":2,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}