{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T11:59:00Z","timestamp":1790078340830,"version":"4.0.1"},"reference-count":39,"publisher":"National Academy of Sciences","issue":"46","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2010,11,16]]},"abstract":"<jats:p>\n                    Ivermectin (IVM) is a broad-spectrum anthelmintic used in filariasis control programs. By binding to nematode glutamate-gated chloride channels (GluCls), IVM disrupts neurotransmission processes regulated by GluCl activity. IVM treatment of filarial infections is characterized by an initial dramatic drop in the levels of circulating microfilariae, followed by long-term suppression of their production, but the drug has little direct effect on microfilariae in culture at pharmacologically relevant concentrations. We localized\n                    <jats:italic>Brugia malayi<\/jats:italic>\n                    GluCl expression solely in a muscle structure that surrounds the microfilarial excretory-secretory (ES) vesicle, which suggests that protein release from the ES vesicle is regulated by GluCl activity. Consistent with this hypothesis, exposure to IVM in vitro decreased the amount of protein released from microfilariae. To better understand the scope of IVM effects on protein release by the parasite, three different expression patterns were identified from immunolocalization assays on a representative group of five microfilarial ES products. Patterns of expression suggest that the ES apparatus is the main source of regulated ES product release from microfilariae, as it is the only compartment that appears to be under neuromuscular control. Our results show that IVM treatment of microfilariae results in a marked reduction of protein release from the ES apparatus. Under in vivo conditions, the rapid microfilarial clearance induced by IVM treatment is proposed to result from suppression of the ability of the parasite to secrete proteins that enable evasion of the host immune system.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1011983107","type":"journal-article","created":{"date-parts":[[2010,11,2]],"date-time":"2010-11-02T01:22:00Z","timestamp":1288660920000},"page":"20120-20125","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":154,"title":["Ivermectin disrupts the function of the excretory-secretory apparatus in microfilariae of\n                    <i>Brugia malayi<\/i>"],"prefix":"10.1073","volume":"107","author":[{"given":"Yovany","family":"Moreno","sequence":"first","affiliation":[{"name":"Institute of Parasitology, McGill University\u2013Macdonald Campus, Sainte Anne de Bellevue, Quebec, Canada H9X 3V9; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph F.","family":"Nabhan","sequence":"additional","affiliation":[{"name":"Institute of Parasitology, McGill University\u2013Macdonald Campus, Sainte Anne de Bellevue, Quebec, Canada H9X 3V9; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Solomon","sequence":"additional","affiliation":[{"name":"Institute of Parasitology, McGill University\u2013Macdonald Campus, Sainte Anne de Bellevue, Quebec, Canada H9X 3V9; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles D.","family":"Mackenzie","sequence":"additional","affiliation":[{"name":"Department of Pathology, Michigan State University, East Lansing, MI 48824"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy G.","family":"Geary","sequence":"additional","affiliation":[{"name":"Institute of Parasitology, McGill University\u2013Macdonald Campus, Sainte Anne de Bellevue, Quebec, Canada H9X 3V9; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2010,11]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"e317","DOI":"10.1371\/journal.pntd.0000317","article-title":"The global programme to eliminate lymphatic filariasis: Health impact after 8 years","volume":"2","author":"Ottesen EA","year":"2008","unstructured":"EA Ottesen, PJ Hooper, M Bradley, G Biswas, The global programme to eliminate lymphatic filariasis: Health impact after 8 years. 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