title: Outer surface protein OspC is an antiphagocytic factor that protects Borrelia burgdorferi from phagocytosis by macrophages.
abstract: Outer surface protein C (OspC) is one of the major lipoproteins expressed on the surface of Borrelia burgdorferi during tick feeding and the early phase of mammalian infection. OspC is required for B. burgdorferi 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 ospC-deficient spirochete could not establish infection in NOD-scid IL2rγ(null) mice that lack B cells, T cells, NK cells, and lytic complement. The ospC 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 ospC mutant to establish infection in vivo. In phagocyte-depleted mice, the ospC mutant was able to colonize the joints and triggered neutrophilia during dissemination. Furthermore, we found that phagocytosis of green fluorescent protein (GFP)-expressing ospC 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 B. burgdorferi 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 ospC mutant and that OspC promotes spirochetes' evasion of macrophages during early Lyme borreliosis.
authors.affiliation: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors.forename: Sebastian E
authors.initials: SE
authors.lastname: Carrasco
authors.affiliation: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors.forename: Bryan
authors.initials: B
authors.lastname: Troxell
authors.affiliation: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors.forename: Youyun
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors.forename: Stephanie L
authors.initials: SL
authors.lastname: Brandt
authors.affiliation: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors.forename: George E
authors.initials: GE
authors.lastname: Sandusky
authors.affiliation: Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors.forename: Keith W
authors.initials: KW
authors.lastname: Condon
authors.affiliation: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, USA hserezan@iupui.edu xfyang@iupui.edu.
authors.forename: C Henrique
authors.initials: CH
authors.lastname: Serezani
authors.affiliation: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, USA hserezan@iupui.edu xfyang@iupui.edu.
authors.forename: X Frank
authors.initials: XF
authors.lastname: Yang
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000276:immunology*; D025065:Borrelia burgdorferi / Q000235:genetics* / Q000276:immunology / Q000472:pathogenicity; D002460:Cell Line; D005260:Female; D015964:Gene Expression Regulation, Bacterial; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D057131:Immune Evasion; D007694:Killer Cells, Natural / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D008193:Lyme Disease / Q000235:genetics / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D017737:Macrophages, Peritoneal / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D009504:Neutrophils / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology / Q000382:microbiology / Q000473:pathology
chemical_list: D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; C079616:OspC protein; D049452:Green Fluorescent Proteins