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U.S.A."],"published-print":{"date-parts":[[2012,1,24]]},"abstract":"<jats:p>\n                    Phagocytosis of\n                    <jats:italic>Borrelia burgdorferi<\/jats:italic>\n                    , the causative agent of Lyme disease, is a poorly understood process, despite its importance during the host immune response to infection.\n                    <jats:italic>B. burgdorferi<\/jats:italic>\n                    has been shown to bind to different receptors on the surface of phagocytic cells, including the \u03b2\n                    <jats:sub>2<\/jats:sub>\n                    integrin, complement receptor 3 (CR3). However, whether these receptors mediate the phagocytosis of the spirochete remains unknown. We now demonstrate that CR3 mediates the phagocytosis of the spirochete by murine macrophages and human monocytes. Interaction of\n                    <jats:italic>B. burgdorferi<\/jats:italic>\n                    with the integrin is not sufficient, however, to internalize the spirochete; phagocytosis requires the interaction of CR3 with the GPI-anchored protein, CD14, independently of TLR\/MyD88-induced or inside-out signals. Interestingly, the absence of CR3 leads to marked increases in the production of TNF in vitro and in vivo, despite reduced spirochetal uptake. Furthermore, the absence of CR3 during infection with\n                    <jats:italic>B. burgdorferi<\/jats:italic>\n                    results in the inefficient control of bacterial burdens in the heart and increased Lyme carditis. Overall, our data identify CR3 as a MyD88-independent phagocytic receptor for\n                    <jats:italic>B. burgdorferi<\/jats:italic>\n                    that also participates in the modulation of the proinflammatory output of macrophages. These data also establish a unique mechanism of CR3-mediated phagocytosis that requires the direct cooperation of GPI-anchored proteins.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1112078109","type":"journal-article","created":{"date-parts":[[2012,1,9]],"date-time":"2012-01-09T20:43:26Z","timestamp":1326141806000},"page":"1228-1232","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":65,"title":["CD14 cooperates with complement receptor 3 to mediate MyD88-independent phagocytosis of\n                    <i>Borrelia burgdorferi<\/i>"],"prefix":"10.1073","volume":"109","author":[{"given":"Kelly L.","family":"Hawley","sequence":"first","affiliation":[{"name":"Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst, MA 01003;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"Chris M.","family":"Olson","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst, MA 01003;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan M.","family":"Iglesias-Pedraz","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst, MA 01003;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicol\u00e1s","family":"Navasa","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst, MA 01003;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge L.","family":"Cervantes","sequence":"additional","affiliation":[{"name":"Departments of bPediatrics,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa J.","family":"Caimano","sequence":"additional","affiliation":[{"name":"Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hooman","family":"Izadi","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst, MA 01003;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin R.","family":"Ingalls","sequence":"additional","affiliation":[{"name":"Boston University School of Medicine, Boston, MA 02118;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Utpal","family":"Pal","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, University of Maryland, College Park, MD 20742; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan C.","family":"Salazar","sequence":"additional","affiliation":[{"name":"Departments of bPediatrics,"},{"name":"Division of Pediatric Infectious Diseases, Connecticut Children's Medical Center, Hartford, CT 06106"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin D.","family":"Radolf","sequence":"additional","affiliation":[{"name":"Departments of bPediatrics,"},{"name":"Medicine, and"},{"name":"Genetics and Developmental Biology, University of Connecticut Health Center, Farmington, CT 06030;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Anguita","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst, MA 01003;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2012,1,9]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-0-387-73960-1_14"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0804111"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00685-06"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.285.5428.736"},{"key":"e_1_3_3_5_2","doi-asserted-by":"crossref","first-page":"2382","DOI":"10.4049\/jimmunol.163.5.2382","article-title":"Cutting edge: Inflammatory signaling by Borrelia burgdorferi lipoproteins is mediated by toll-like receptor 2","volume":"163","author":"Hirschfeld M","year":"1999","unstructured":"M Hirschfeld, et al., Cutting edge: Inflammatory signaling by Borrelia burgdorferi lipoproteins is mediated by toll-like receptor 2. 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