{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T19:52:04Z","timestamp":1792525924201,"version":"4.5.0"},"reference-count":48,"publisher":"The Company of Biologists","issue":"14","license":[{"start":{"date-parts":[[2023,7,28]],"date-time":"2023-07-28T00:00:00Z","timestamp":1690502400000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["K08 AI103036"],"award-info":[{"award-number":["K08 AI103036"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01 AI146349-S1"],"award-info":[{"award-number":["R01 AI146349-S1"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01 AI146349"],"award-info":[{"award-number":["R01 AI146349"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Children's Clinical Research Advisory Committee"},{"name":"I-2086"},{"DOI":"10.13039\/100000928","name":"Welch Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000928","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100007914","name":"University of Texas Southwestern Medical Center","doi-asserted-by":"crossref","award":["NIH T32GM008014"],"award-info":[{"award-number":["NIH T32GM008014"]}],"id":[{"id":"10.13039\/100007914","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100012645","name":"University of Texas at Dallas","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100012645","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100017189","name":"Cecil and Ida Green Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100017189","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,7,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>Leishmania spp. are obligate intracellular parasites that must be internalized by phagocytic cells to evade immune responses and cause disease. The uptake of both Leishmania promastigotes (insect-stage parasites) and amastigotes (proliferative-stage parasites in humans and mice) by phagocytes is thought to be mainly host cell driven, not parasite driven. Our previous work indicates that host Src- and Abl-family kinases facilitate Leishmania entry into macrophages and pathogenesis in murine cutaneous leishmaniasis. Here, we demonstrate that host spleen tyrosine kinase (SYK) is required for efficient uptake of Leishmania promastigotes and amastigotes. A Src-family kinase\u2013Abl-family kinase\u2013SYK signaling cascade induces Leishmania amastigote internalization. Finally, lesion size and parasite burden during Leishmania infection is significantly decreased in mice lacking SYK in monocytes or by treatment with the SYK inhibitor entospletinib. In summary, SYK is required for maximal Leishmania uptake by macrophages and disease in mice. Our results suggest potential for treating leishmaniasis using host cell-directed agents.<\/jats:p>","DOI":"10.1242\/jcs.260809","type":"journal-article","created":{"date-parts":[[2023,6,26]],"date-time":"2023-06-26T07:36:37Z","timestamp":1687764997000},"source":"Crossref","is-referenced-by-count":9,"title":["Src- and Abl-family kinases activate spleen tyrosine kinase to maximize phagocytosis and <i>Leishmania<\/i> infection"],"prefix":"10.1242","volume":"136","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1432-1705","authenticated-orcid":false,"given":"Imran","family":"Ullah","sequence":"first","affiliation":[{"name":"University of Texas Southwestern Medical Center 1 Department of Pediatrics , , 5323 Harry Hines Blvd, Dallas, TX 75390 , USA"},{"name":"University of Texas Southwestern Medical Center 2 Department of Biochemistry , , 5323 Harry Hines Blvd, Dallas, TX 75390 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0365-7070","authenticated-orcid":false,"given":"Umaru","family":"Barrie","sequence":"additional","affiliation":[{"name":"University of Texas Southwestern Medical Center 1 Department of Pediatrics , , 5323 Harry Hines Blvd, Dallas, TX 75390 , USA"},{"name":"University of Texas Southwestern Medical Center 3 Medical Scientist Training Program , , 5323 Harry Hines Blvd, Dallas, TX 75390 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca M.","family":"Kernen","sequence":"additional","affiliation":[{"name":"University of Texas Southwestern Medical Center 1 Department of Pediatrics , , 5323 Harry Hines Blvd, Dallas, TX 75390 , USA"},{"name":"University of Texas Southwestern Medical Center 4 Emergency Medicine Residency Program , , 5323 Harry Hines Blvd, Dallas, TX 75390 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily T.","family":"Mamula","sequence":"additional","affiliation":[{"name":"University of Texas Southwestern Medical Center 1 Department of Pediatrics , , 5323 Harry Hines Blvd, Dallas, TX 75390 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6566-1657","authenticated-orcid":false,"given":"Francis Tho Huu","family":"Khuong","sequence":"additional","affiliation":[{"name":"University of Texas Southwestern Medical Center 1 Department of Pediatrics , , 5323 Harry Hines Blvd, Dallas, TX 75390 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0175-9468","authenticated-orcid":false,"given":"Laela M.","family":"Booshehri","sequence":"additional","affiliation":[{"name":"University of Texas Southwestern Medical Center 1 Department of Pediatrics , , 5323 Harry Hines Blvd, Dallas, TX 75390 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9994-3898","authenticated-orcid":false,"given":"Emma L.","family":"Rhodes","sequence":"additional","affiliation":[{"name":"University of Texas Southwestern Medical Center 1 Department of Pediatrics , , 5323 Harry Hines Blvd, Dallas, TX 75390 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0730-152X","authenticated-orcid":false,"given":"James M.","family":"Bradford","sequence":"additional","affiliation":[{"name":"University of Texas Southwestern Medical Center 1 Department of Pediatrics , , 5323 Harry Hines Blvd, Dallas, TX 75390 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2459-5964","authenticated-orcid":false,"given":"Arani","family":"Datta","sequence":"additional","affiliation":[{"name":"University of Texas Southwestern Medical Center 1 Department of Pediatrics , , 5323 Harry Hines Blvd, Dallas, TX 75390 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3990-7043","authenticated-orcid":false,"given":"Dawn M.","family":"Wetzel","sequence":"additional","affiliation":[{"name":"University of Texas Southwestern Medical Center 1 Department of Pediatrics , , 5323 Harry Hines Blvd, Dallas, TX 75390 , USA"},{"name":"University of Texas Southwestern Medical Center 2 Department of Biochemistry , , 5323 Harry Hines Blvd, Dallas, TX 75390 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2023,7,28]]},"reference":[{"key":"2023072810231226400_JCS260809C1","doi-asserted-by":"publisher","first-page":"1244","DOI":"10.1038\/s41467-021-21360-8","article-title":"Systematic functional analysis of Leishmania protein kinases identifies regulators of differentiation or survival","volume":"12","author":"Baker","year":"2021","journal-title":"Nat. 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