{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T02:54:24Z","timestamp":1760237664132,"version":"build-2065373602"},"reference-count":52,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2020,6,4]],"date-time":"2020-06-04T00:00:00Z","timestamp":1591228800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"International Science and Technology Cooperation Project of Gansu Provincial Key Research and Development Program","award":["Grant No. 17JR7WA031"],"award-info":[{"award-number":["Grant No. 17JR7WA031"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Central to the progression of cerebral toxoplasmosis is the interaction of Toxoplasma gondii with the blood-brain barrier (BBB) endothelial cells. In the present work, we tested the hypothesis that inhibition of Wnt pathway signalling by the monovalent ionophore monensin reduces the growth of T. gondii infecting human brain microvascular endothelial cells (hBMECs) or microglial cells. The anti-parasitic effect of monensin (a Wnt signalling inhibitor) on the in vitro growth of T. gondii tachyzoites was investigated using two methods (Sulforhodamine B staining and microscopic parasite counting). The monensin inhibited T. gondii growth (50% inhibitory concentration [IC50] = 0.61 \u03bcM) with a selective index = 8.48 when tested against hBMECs (50% cytotoxic concentration [CC50] = 5.17 \u03bcM). However, IC50 of monensin was 4.13 \u03bcM with a SI = 13.82 when tested against microglia cells (CC50 = 57.08 \u03bcM), suggesting less sensitivity of microglia cells to monensin treatment. The effect of T. gondii on the integrity of the BBB was assessed by the transendothelial electrical resistance (TEER) assay using an in vitro human BBB model. The results showed that T. gondii infection significantly decreased hBMECs\u2019 TEER resistance, which was rescued when cells were treated with 0.1 \u00b5M monensin, probably due to the anti-parasitic activity of monensin. We also investigated the host-targeted effects of 0.1 \u00b5M monensin on global gene expression in hBMECs with or without T. gondii infection. Treatment of hBMECs with monensin did not significantly influence the expression of genes involved in the Wnt signalling pathway, suggesting that although inhibition of the Wnt signalling pathway did not play a significant role in T. gondii infection of hBMECs, monensin was still effective in limiting the growth of T. gondii. On the contrary, monensin treatment downregulated pathways related to steroids, cholesterol and protein biosynthesis and their transport between endoplasmic reticulum and Golgi apparatus, and deregulated pathways related to cell cycle and DNA synthesis and repair mechanisms. These results provide new insight into the host-modulatory effect of monensin during T. gondii infection, which merits further investigation.<\/jats:p>","DOI":"10.3390\/microorganisms8060842","type":"journal-article","created":{"date-parts":[[2020,6,5]],"date-time":"2020-06-05T03:32:21Z","timestamp":1591327941000},"page":"842","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Transcriptome Profiling of Toxoplasma gondii-Infected Human Cerebromicrovascular Endothelial Cell Response to Treatment with Monensin"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3067-4132","authenticated-orcid":false,"given":"Mohammad S. R.","family":"Harun","sequence":"first","affiliation":[{"name":"Infectomics Cluster, Advanced Medical &amp; Dental Institute, Universiti Sains Malaysia, Bertam, Kepala Batas, Pulau Pinang 13200, Malaysia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mica","family":"Taylor","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Health Sciences, School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington Campus, Loughborough LE12 5RD, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2530-4628","authenticated-orcid":false,"given":"Xing-Quan","family":"Zhu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Veterinary Etiological Biology, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3303-930X","authenticated-orcid":false,"given":"Hany M.","family":"Elsheikha","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Health Sciences, School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington Campus, Loughborough LE12 5RD, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,6,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1965","DOI":"10.1016\/S0140-6736(04)16412-X","article-title":"Toxoplasmosis","volume":"363","author":"Montoya","year":"2004","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/j.puhe.2007.08.009","article-title":"Congenital toxoplasmosis: Priorities for further health promotion action","volume":"122","author":"Elsheikha","year":"2008","journal-title":"Public Health"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1016\/S0020-7519(00)00124-7","article-title":"Toxoplasma gondii: From animals to humans","volume":"30","author":"Tenter","year":"2000","journal-title":"Int. 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