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Host protection likely acts at both cellular levels to control the parasite. CD40 is a key factor for protection against cerebral and ocular toxoplasmosis. We determined if CD40 induces anti-<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">T. gondii<\/jats:named-content>activity at the level of nonhematopoietic cells. Engagement of CD40 on various endothelial cells including human microvascular brain endothelial cells, human umbilical vein endothelial cells, and a mouse endothelial cell line as well as human and mouse retinal pigment epithelial cells resulted in killing of<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">T. gondii<\/jats:named-content>. CD40 stimulation increased expression of the autophagy proteins Beclin 1 and LC3 II, enhanced autophagy flux, and led to recruitment of LC3 around the parasite. The late endosomal\/lysosomal marker LAMP-1 accumulated around the parasite in CD40-stimulated cells. This was accompanied by killing of<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">T. gondii<\/jats:named-content>dependent on lysosomal enzymes. Accumulation of LAMP-1 and killing of<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">T. gondii<\/jats:named-content>were dependent on the autophagy proteins Beclin 1 and Atg7. Together, these studies revealed that CD40 induces toxoplasmacidal activity in various nonhematopoietic cells dependent on proteins of the autophagy machinery.<\/jats:p>","DOI":"10.1128\/iai.01145-12","type":"journal-article","created":{"date-parts":[[2013,3,19]],"date-time":"2013-03-19T04:03:09Z","timestamp":1363665789000},"page":"2002-2011","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":66,"title":["CD40 Induces Anti-Toxoplasma gondii Activity in Nonhematopoietic Cells Dependent on Autophagy Proteins"],"prefix":"10.1128","volume":"81","author":[{"given":"Jennifer","family":"Van Grol","sequence":"first","affiliation":[{"name":"Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA"},{"name":"Division of Infectious Diseases and HIV Medicine, Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"Muniz-Feliciano","sequence":"additional","affiliation":[{"name":"Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA"},{"name":"Division of Infectious Diseases and HIV Medicine, Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose-Andres C.","family":"Portillo","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and HIV Medicine, Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vera L.","family":"Bonilha","sequence":"additional","affiliation":[{"name":"The Cole Eye Institute, Department of Ophthalmic Research, Cleveland Clinic, Cleveland, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos S.","family":"Subauste","sequence":"additional","affiliation":[{"name":"Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA"},{"name":"Division of Infectious Diseases and HIV Medicine, Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA"},{"name":"Department of Ophthalmology and Visual Sciences, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.83.12.4494"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.178.2.669"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.182.1.33"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.169.6.2043"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/357080a0"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1992.tb05530.x"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/35393"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830250639"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90668-G"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(97)70123-9"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.md.0000100046.06009.b0"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(03)00324-8"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80436-7"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80434-3"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80435-5"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.68.3.1312-1318.2000"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0014472"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.66.2.603-607.1998"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.67.10.5253-5257.1999"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI28796"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2009.10.007"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01068-08"},{"key":"e_1_3_2_24_2","first-page":"1921","article-title":"Mice that exclusively express TLR4 on endothelial cells can efficiently clear a lethal systemic Gram-negative bacterial infection","volume":"119","author":"Andonegui G","year":"2009","unstructured":"AndoneguiGZhouHBullardDKellyMMMullalySCMcDonaldBLongEMRobbinsSMKubesP. 2009. 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