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THP-1 monocytoid cells were activated to comparable extents by live<jats:italic>Borrelia burgdorferi<\/jats:italic>and by<jats:italic>B. burgdorferi<\/jats:italic>and<jats:italic>Treponema pallidum<\/jats:italic>lysates but were poorly activated by live<jats:italic>T. pallidum<\/jats:italic>. Because THP-1 cells poorly internalized live spirochetes, we turned to an ex vivo peripheral blood mononuclear cell system that would more closely reflect spirochete-mononuclear phagocyte interactions that occur during actual infection. In this system,<jats:italic>B. burgdorferi<\/jats:italic>induced significantly greater monocyte activation and inflammatory cytokine production than did borrelial lysates or<jats:italic>T. pallidum<\/jats:italic>, and only<jats:italic>B. burgdorferi<\/jats:italic>elicited gamma interferon (IFN-\u03b3) from NK cells.<jats:italic>B. burgdorferi<\/jats:italic>was phagocytosed avidly by monocytes, while<jats:italic>T. pallidum<\/jats:italic>was not, suggesting that the enhanced response to live<jats:italic>B. burgdorferi<\/jats:italic>was due to phagocytosis of the organism. When cytochalasin D was used to block phagocytosis of live<jats:italic>B. burgdorferi<\/jats:italic>, cytokine production decreased to levels comparable to those induced by<jats:italic>B. burgdorferi<\/jats:italic>lysates, while the IFN-\u03b3 response was abrogated altogether. In the presence of human syphilitic serum,<jats:italic>T. pallidum<\/jats:italic>was efficiently internalized and initiated responses resembling those observed with live<jats:italic>B. burgdorferi<\/jats:italic>, including the production of IFN-\u03b3 by NK cells. Depletion of monocytes revealed that they were the primary source of inflammatory cytokines, while dendritic cells (DCs) directed IFN-\u03b3 production from innate lymphocytes. Thus, phagocytosis of live spirochetes initiates cell activation programs in monocytes and DCs that differ qualitatively and quantitatively from those induced at the cell surface by lipoprotein-enriched lysates. The greater stimulatory capacity of<jats:italic>B. burgdorferi<\/jats:italic>versus<jats:italic>T. pallidum<\/jats:italic>appears to be explained by the successful recognition and phagocytosis of<jats:italic>B. burgdorferi<\/jats:italic>by host cells and the ability of<jats:italic>T. pallidum<\/jats:italic>to avoid detection and uptake by virtue of its denuded outer membrane rather than by differences in surface lipoprotein expression.<\/jats:p>","DOI":"10.1128\/iai.01666-06","type":"journal-article","created":{"date-parts":[[2007,1,13]],"date-time":"2007-01-13T01:48:47Z","timestamp":1168652927000},"page":"2046-2062","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":100,"title":["Phagocytosis of<i>Borrelia burgdorferi<\/i>and<i>Treponema pallidum<\/i>Potentiates Innate Immune Activation and Induces Gamma Interferon Production"],"prefix":"10.1128","volume":"75","author":[{"given":"Meagan W.","family":"Moore","sequence":"first","affiliation":[{"name":"Departments of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana R.","family":"Cruz","sequence":"additional","affiliation":[{"name":"Departments of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carson J.","family":"LaVake","sequence":"additional","affiliation":[{"name":"Departments of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda L.","family":"Marzo","sequence":"additional","affiliation":[{"name":"Departments of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian H.","family":"Eggers","sequence":"additional","affiliation":[{"name":"Departments of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan C.","family":"Salazar","sequence":"additional","affiliation":[{"name":"Division of Pediatric Infectious Diseases, Department of Pediatrics, Connecticut Children's Medical Center, Hartford, Connecticut 06106"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin D.","family":"Radolf","sequence":"additional","affiliation":[{"name":"Departments of Medicine"},{"name":"Genetics and Developmental Biology, University of Connecticut Health Center, Farmington, Connecticut 06030-3715"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/1521-4141(200207)32:7<1958::AID-IMMU1958>3.0.CO;2-U"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.02.015"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm732"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.285.5428.736"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20051782"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-695X.1993.tb00339.x"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.18.1.767"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/150.4.497"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.17.1.189"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature04596"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.285.5428.732"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.67.7.3329-3333.1999"},{"key":"e_1_3_2_14_2","first-page":"237","year":"2006","unstructured":"Cameron, C. 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