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Uptake of borreliae by immune cells is decisive for the course of the infection, and remodelling of the host actin cytoskeleton is crucial in this process. In this study, we showed that the actin\u2010regulatory formin Daam1 is important in\n                    <jats:italic>Borrelia<\/jats:italic>\n                    phagocytosis by primary human macrophages. Uptake of borreliae proceeds preferentially through capture by filopodia and formation of coiling pseudopods that enwrap the spirochetes. Using immunofluorescence, we localized endogenous and overexpressed Daam1 to filopodia and to F\u2010actin\u2010rich uptake structures. Live\u2010cell imaging further showed that Daam1 is enriched at coiling pseudopods that arise from the macrophage surface. This filopodia\u2010independent step was corroborated by control experiments of phagocytic cup formation with latex beads. Moreover, siRNA\u2010mediated knockdown of Daam1 led to a 65% reduction of borreliae\u2010induced filopodia, and, as shown by the outside\u2013inside staining technique, to a 50% decrease in phagocytic uptake of borreliae, as well as a 37% reduction in coiling pseudopod formation. Collectively, we showed that Daam1 plays a dual role in the phagocytic uptake of borreliae: first, as a regulator of filopodia, which are used for capturing spirochetes, and second, in the formation of the coiling pseudopod that enwraps the bacterial cell. These data identify Daam1 as a novel regulator of\n                    <jats:italic>B. burgdorferi<\/jats:italic>\n                    phagocytosis. At the same time, this is the first demonstration of a role for Daam1 in phagocytic processes in general.\u2014Hoffmann, A.\u2010K., Naj, X., Linder, S. Daam1 is a regulator of filopodia formation and phagocytic uptake of\n                    <jats:italic>Borrelia burgdorferi<\/jats:italic>\n                    by primary human macrophages.\n                    <jats:italic>FASEB J<\/jats:italic>\n                    . 28, 3075\u20133089 (2014).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.13-247049","type":"journal-article","created":{"date-parts":[[2014,4,2]],"date-time":"2014-04-02T23:18:32Z","timestamp":1396480712000},"page":"3075-3089","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Daam1 is a regulator of filopodia formation and phagocytic uptake of\n                    <i>Borrelia burgdorferi<\/i>\n                    by primary human macrophages"],"prefix":"10.1096","volume":"28","author":[{"given":"Ann\u2010Kathrin","family":"Hoffmann","sequence":"first","affiliation":[{"name":"Institute for Medical Microbiology, Virology, and Hygiene University Medical Center Eppendorf Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xenia","family":"Naj","sequence":"additional","affiliation":[{"name":"Institute for Medical Microbiology, Virology, and Hygiene University Medical Center Eppendorf Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Linder","sequence":"additional","affiliation":[{"name":"Institute for Medical Microbiology, Virology, and Hygiene University Medical Center Eppendorf Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,4,2]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.meegid.2011.07.022"},{"key":"e_1_2_7_3_1","first-page":"181","article-title":"[The analysis of epidemiology, clinical symptoms, serological tests in the course of borreliosis]","volume":"67","author":"Biesiada G.","year":"2010","journal-title":"Przegl. 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