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We examined the effects of endothelial cell EGFR on CNS invasion. Transgenic mice whose endothelial cells expressed a dominant negative (DN) EGFR (inhibits EGFR signaling) exhibited diminished parasite load and histopathology in the brain and retina after<jats:italic>T. gondii<\/jats:italic>infection. I.V. administration of infected leukocytes or extracellular tachyzoites led to reduced parasite loads in mice with DN EGFR. This was not explained by enhanced immunity or reduced leukocyte recruitment. Endothelial cell infection is key for CNS invasion. Parasite foci in brain endothelial cells were reduced by DN EGFR. DN EGFR in these cells led to recruitment of the autophagy protein LC3 around<jats:italic>T. gondii<\/jats:italic>and spontaneous parasite killing dependent on the autophagy protein ULK1 and lysosomal enzymes. The autophagy inhibitor 3-MA prevented DN EGFR mice from exhibiting reduced CNS invasion. Altogether, EGFR is a novel regulator of<jats:italic>T. gondii<\/jats:italic>invasion of neural tissue, enhancing invasion likely by promoting survival of the parasite within endothelial cells.<\/jats:p>","DOI":"10.1038\/s41598-018-36724-2","type":"journal-article","created":{"date-parts":[[2019,1,24]],"date-time":"2019-01-24T11:04:17Z","timestamp":1548327857000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Epidermal growth factor receptor promotes cerebral and retinal invasion by Toxoplasma gondii"],"prefix":"10.1038","volume":"9","author":[{"given":"Yalitza Lopez","family":"Corcino","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose-Andres C.","family":"Portillo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5602-1439","authenticated-orcid":false,"given":"Carlos S.","family":"Subauste","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,1,24]]},"reference":[{"key":"36724_CR1","doi-asserted-by":"publisher","first-page":"1965","DOI":"10.1016\/S0140-6736(04)16412-X","volume":"363","author":"JG Montoya","year":"2004","unstructured":"Montoya, J. 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