{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T07:44:45Z","timestamp":1780991085121,"version":"3.54.1"},"update-to":[{"DOI":"10.1371\/journal.pntd.0010474","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,6,17]],"date-time":"2022-06-17T00:00:00Z","timestamp":1655424000000}}],"reference-count":65,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2022,6,7]],"date-time":"2022-06-07T00:00:00Z","timestamp":1654560000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000849","name":"National Centre for the Replacement, Refinement and Reduction of Animals in Research","doi-asserted-by":"publisher","award":["NC\/M00175X\/1"],"award-info":[{"award-number":["NC\/M00175X\/1"]}],"id":[{"id":"10.13039\/501100000849","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["BMGF OPP1054324"],"award-info":[{"award-number":["BMGF OPP1054324"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:p>The development of new drugs targeting adult-stage lymphatic filarial nematodes is hindered by the lack of a robust long-term<jats:italic>in vitro<\/jats:italic>culture model. Testing potential direct-acting and anti-<jats:italic>Wolbachia<\/jats:italic>therapeutic candidates against adult lymphatic filariae<jats:italic>in vitro<\/jats:italic>requires their propagation via chronic infection of gerbils. We evaluated<jats:italic>Brugia malayi<\/jats:italic>parasite burden data from male Mongolian gerbils compared with two immune-deficient mouse strains highly susceptible to<jats:italic>B<\/jats:italic>.<jats:italic>malayi<\/jats:italic>: CB.17 Severe-Combined Immmuno-Deficient (SCID) and interleukin-4 receptor alpha, interleukin-5 double knockout (IL-4R\u03b1<jats:sup>-\/-<\/jats:sup>IL-5<jats:sup>-\/-<\/jats:sup>) mice. Adult worms generated in IL-4R\u03b1<jats:sup>-\/-<\/jats:sup>IL-5<jats:sup>-\/-<\/jats:sup>mice were tested with different feeder cells (human embryonic kidney cells, human adult dermal lymphatic endothelial cells and human THP-1 monocyte differentiated macrophages) and comparative cell-free conditions to optimise and validate a long-term<jats:italic>in vitro<\/jats:italic>culture system. Cultured parasites were compared against those isolated from mice using motility scoring, metabolic viability assay (MTT),<jats:italic>ex vivo<\/jats:italic>microfilariae release assay and<jats:italic>Wolbachia<\/jats:italic>content by qPCR. A selected culture system was validated as a drug screen using reference anti-<jats:italic>Wolbachia<\/jats:italic>(doxycycline, ABBV-4083 \/ flubentylosin) or direct-acting compounds (flubendazole, suramin). BALB\/c IL-4R\u03b1<jats:sup>-\/-<\/jats:sup>IL-5<jats:sup>-\/-<\/jats:sup>or CB.17 SCID mice were superior to Mongolian gerbils in generating adult worms and supporting<jats:italic>in vivo<\/jats:italic>persistence for periods of up to 52 weeks. Adult females retrieved from BALB\/c IL-4R\u03b1<jats:sup>-\/-<\/jats:sup>IL-5<jats:sup>-\/-<\/jats:sup>mice could be cultured for up to 21 days in the presence of a lymphatic endothelial cell co-culture system with comparable motility, metabolic activity and<jats:italic>Wolbachia<\/jats:italic>titres to those maintained<jats:italic>in vivo<\/jats:italic>. Drug studies confirmed significant<jats:italic>Wolbachia<\/jats:italic>depletions or direct macrofilaricidal activities could be discerned when female<jats:italic>B<\/jats:italic>.<jats:italic>malayi<\/jats:italic>were cultured for 14 days. We therefore demonstrate a novel methodology to generate adult<jats:italic>B<\/jats:italic>.<jats:italic>malayi in vivo<\/jats:italic>and accurately evaluate drug efficacy<jats:italic>ex vivo<\/jats:italic>which may be adopted for drug screening with the dual benefit of reducing overall animal use and improving anti-filarial drug development.<\/jats:p>","DOI":"10.1371\/journal.pntd.0010474","type":"journal-article","created":{"date-parts":[[2022,6,7]],"date-time":"2022-06-07T17:46:51Z","timestamp":1654624011000},"page":"e0010474","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["A mouse infection model and long-term lymphatic endothelium co-culture system to evaluate drugs against adult Brugia malayi"],"prefix":"10.1371","volume":"16","author":[{"given":"Amy E.","family":"Marriott","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julio","family":"Furlong 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