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OspC is required for<jats:named-content content-type=\"genus-species\">B. burgdorferi<\/jats:named-content>to establish infection in both immunocompetent and SCID mice and has been proposed to facilitate evasion of innate immune defenses. However, the exact biological function of OspC remains elusive. In this study, we showed that the<jats:italic>ospC<\/jats:italic>-deficient spirochete could not establish infection in NOD-<jats:italic>scid IL2r<\/jats:italic>\u03b3<jats:sup>null<\/jats:sup>mice that lack B cells, T cells, NK cells, and lytic complement. The<jats:italic>ospC<\/jats:italic>mutant also could not establish infection in anti-Ly6G-treated SCID and C3H\/HeN mice (depletion of neutrophils). However, depletion of mononuclear phagocytes at the skin site of inoculation in SCID and C3H\/HeN mice allowed the<jats:italic>ospC<\/jats:italic>mutant to establish infection<jats:italic>in vivo<\/jats:italic>. In phagocyte-depleted mice, the<jats:italic>ospC<\/jats:italic>mutant was able to colonize the joints and triggered neutrophilia during dissemination. Furthermore, we found that phagocytosis of green fluorescent protein (GFP)-expressing<jats:italic>ospC<\/jats:italic>mutant spirochetes by murine peritoneal macrophages and human THP-1 macrophage-like cells, but not in PMN-HL60, was significantly higher than parental wild-type<jats:named-content content-type=\"genus-species\">B. burgdorferi<\/jats:named-content>strains, suggesting that OspC has an antiphagocytic property. In addition, overproduction of OspC in spirochetes also decreased the uptake of spirochetes by murine peritoneal macrophages. Together, our findings provide evidence that mononuclear phagocytes play a key role in clearance of the<jats:italic>ospC<\/jats:italic>mutant and that OspC promotes spirochetes' evasion of macrophages during early Lyme borreliosis.<\/jats:p>","DOI":"10.1128\/iai.01215-15","type":"journal-article","created":{"date-parts":[[2015,10,6]],"date-time":"2015-10-06T00:11:36Z","timestamp":1444090296000},"page":"4848-4860","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":83,"title":["Outer Surface Protein OspC Is an Antiphagocytic Factor That Protects Borrelia burgdorferi from Phagocytosis by Macrophages"],"prefix":"10.1128","volume":"83","author":[{"given":"Sebastian E.","family":"Carrasco","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan","family":"Troxell","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youyun","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie L.","family":"Brandt","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongxia","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George E.","family":"Sandusky","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith W.","family":"Condon","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, Indiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. 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