{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T18:26:01Z","timestamp":1787163961651,"version":"build-2736575974"},"reference-count":107,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institute of Health Research","doi-asserted-by":"crossref","award":["PJT-162191"],"award-info":[{"award-number":["PJT-162191"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["RGPIN-2018-04991"],"award-info":[{"award-number":["RGPIN-2018-04991"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000233","name":"Genome British Columbia","doi-asserted-by":"publisher","award":["264PRO"],"award-info":[{"award-number":["264PRO"]}],"id":[{"id":"10.13039\/501100000233","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    Protozoan parasites of the genus\n                    <jats:italic>Leishmania,<\/jats:italic>\n                    the causative agents of human leishmaniasis, have evolved mechanisms to manipulate host cell functions to their advantage. Recently, small non-coding RNAs have been identified as contributors to the pathogenesis of\n                    <jats:italic>Leishmania<\/jats:italic>\n                    infection. An increasing number of studies have demonstrated that\n                    <jats:italic>Leishmania<\/jats:italic>\n                    tRNA-derived small non-coding RNAs, also known as\n                    <jats:italic>Leishmania<\/jats:italic>\n                    tRNA-derived fragments (Ld-tRFs), can be delivered to host cells via exosomes, thereby influencing host cell function. Here, we investigated the potential effects of\n                    <jats:italic>Leishmania<\/jats:italic>\n                    exosomal Ld-tRF-Asp and Ld-tRF-Leu in THP-1-derived host macrophages. SILAC (Stable Isotope Labelling by Amino acids in Cell culture) based quantitative proteomics was used to investigate the effects of synthetic Ld-tRF-Asp and Ld-tRF-Leu by analyzing how these Ld-tRFs affect the macrophage proteome. Ld-tRF-Asp modulated 20 proteins, whereas Ld-tRF-Leu affected 18 proteins in macrophages. Interestingly, 7 of the Ld-tRF-Asp-modulated proteins and 7 of the Ld-tRF-Leu-modulated proteins showed potential pro-\n                    <jats:italic>Leishmania<\/jats:italic>\n                    effects. Biochemical isolation of Argonaute (Ago) protein complexes by \u201cAgo proteins Affinity Purification by Peptide,\u201d followed by identification of interacting small non-coding RNAs, revealed the selective presence of both tRFs in\n                    <jats:italic>Leishmania-<\/jats:italic>\n                    infected macrophages. This striking finding suggested that Ld-tRFs engage macrophage Ago proteins for their effects. In addition, an\n                    <jats:italic>in vivo<\/jats:italic>\n                    biotin-RNA pull-down assay showed that Ld-tRF-Leu selectively interacted with Ago 1, suggesting that Ago 1 is the preferred Ago guiding Ld-tRFs to target host genes. Taken together, this study shows, for the first time, that\n                    <jats:italic>Leishmania<\/jats:italic>\n                    exosomal tRFs significantly alter the host macrophage proteome in favour of\n                    <jats:italic>Leishmania<\/jats:italic>\n                    survival. This may offer new insights into the mechanisms of leishmaniasis and may provide future therapeutic interventions targeting these regulatory molecules.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0356144","type":"journal-article","created":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T17:39:37Z","timestamp":1787161177000},"page":"e0356144","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Leishmania exosomal tRNA-derived small non-coding RNA fragments modulate host THP-1 derived macrophage proteins: A quantitative proteomic analysis"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6768-2777","authenticated-orcid":true,"given":"Harsimran Kaur","family":"Brar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6322-6344","authenticated-orcid":true,"given":"Atieh","family":"Moradimotlagh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dilraj Kaur","family":"Longowal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3796-720X","authenticated-orcid":true,"given":"Kyung-Mee","family":"Moon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8551-4817","authenticated-orcid":true,"given":"Leonard J.","family":"Foster","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice L-F","family":"Mui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil","family":"Reiner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6332-4841","authenticated-orcid":true,"given":"Devki","family":"Nandan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,8,19]]},"reference":[{"issue":"2","key":"pone.0356144.ref001","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1007\/s40475-021-00232-7","article-title":"A Review of Leishmaniasis: Current Knowledge and Future Directions","volume":"8","author":"S Mann","year":"2021","journal-title":"Curr Trop Med Rep"},{"issue":"4","key":"pone.0356144.ref002","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1093\/labmed\/lmac134","article-title":"Review of the Clinical Presentation, 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