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As for metastatic cells, recent paradigms of leukocyte migration attribute important roles to the amoeboid migration mode of dendritic cells (DCs) for rapid locomotion in tissues. However, the role of TIMP-1 in immune cell migration and in the context of infection has not been addressed. We report that, upon challenge with the obligate intracellular parasite Toxoplasma gondii, primary DCs secrete TIMP-1 with implications for their migratory properties. Using a short hairpin RNA (shRNA) gene silencing approach, we demonstrate that secreted TIMP-1 and its ligand CD63 are required for the onset of hypermotility in DCs challenged with T. gondii. Further, gene silencing and antibody blockade of the \u03b21-integrin CD29 (ITGB1) inhibited DC hypermotility, indicating that signal transduction occurred via ITGB1. Finally, gene silencing of the ITGB1-associated focal adhesion kinase (FAK, also known as PTK2), as well as pharmacological antagonism of FAK and associated kinases SRC and PI3K, abrogated hypermotility. The present study identifies a TIMP-1\u2013CD63\u2013ITGB1\u2013FAK signaling axis in primary DCs, which T. gondii hijacks to drive high-speed amoeboid migration of the vehicle cells that facilitate its systemic dissemination.<\/jats:p>","DOI":"10.1242\/jcs.225193","type":"journal-article","created":{"date-parts":[[2019,1,11]],"date-time":"2019-01-11T14:40:01Z","timestamp":1547217601000},"source":"Crossref","is-referenced-by-count":34,"title":["TIMP-1 promotes hypermigration of <i>Toxoplasma<\/i>-infected primary dendritic cells via CD63\u2013ITGB1\u2013FAK signaling"],"prefix":"10.1242","volume":"132","author":[{"given":"Einar B.","family":"\u00d3lafsson","sequence":"first","affiliation":[{"name":"The Wenner-Gren Institute, Stockholm University 1 Department of Molecular Biosciences , , 106 09 Stockholm , Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily C.","family":"Ross","sequence":"additional","affiliation":[{"name":"The Wenner-Gren Institute, Stockholm University 1 Department of Molecular Biosciences , , 106 09 Stockholm , Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Varas-Godoy","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica 2 , Faculty of Medicine , , 7620001 Santiago , Chile"},{"name":"Universidad de los Andes 2 , Faculty of Medicine , , 7620001 Santiago , Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7746-9964","authenticated-orcid":false,"given":"Antonio","family":"Barragan","sequence":"additional","affiliation":[{"name":"The Wenner-Gren Institute, Stockholm University 1 Department of Molecular Biosciences , , 106 09 Stockholm , Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2019,2,4]]},"reference":[{"key":"2024061318195338600_JCS225193C1","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1016\/j.immuni.2008.08.006","article-title":"Mechanisms and consequences of dendritic cell migration","volume":"29","author":"Alvarez","year":"2008","journal-title":"Immunity"},{"key":"2024061318195338600_JCS225193C2","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1038\/onc.2017.321","article-title":"Tissue inhibitor of metalloproteinase-1 promotes cell proliferation through YAP\/TAZ activation in cancer","volume":"37","author":"Ando","year":"2018","journal-title":"Oncogene"},{"key":"2024061318195338600_JCS225193C3","doi-asserted-by":"publisher","first-page":"8485","DOI":"10.4049\/jimmunol.181.12.8485","article-title":"Dendritic cells expressing plasmacytoid marker PDCA-1 are Trojan horses during Toxoplasma gondii infection","volume":"181","author":"Bierly","year":"2008","journal-title":"J. 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