Outer surface protein OspC is an antiphagocytic factor that protects Borrelia burgdorferi from phagocytosis by macrophages

• Published in: Infection and immunity 2015-12, Vol.83 (12), p.4848-4860
• Main Authors: Carrasco, Sebastian E, Troxell, Bryan, Yang, Youyun, Brandt, Stephanie L, Li, Hongxia, Sandusky, George E, Condon, Keith W, Serezani, C Henrique, Yang, X Frank
• Format: Article
• Language: English
• Subjects: Animals; Antigens, Bacterial - genetics; Antigens, Bacterial - immunology; B-Lymphocytes - immunology; B-Lymphocytes - microbiology; B-Lymphocytes - pathology; Bacterial Outer Membrane Proteins - genetics; Bacterial Outer Membrane Proteins - immunology; Borrelia burgdorferi - genetics; Borrelia burgdorferi - immunology; Borrelia burgdorferi - pathogenicity; Cell Line; Female; Gene Expression Regulation, Bacterial; Genes, Reporter; Green Fluorescent Proteins - genetics; Green Fluorescent Proteins - metabolism; Humans; Immune Evasion; Killer Cells, Natural - immunology; Killer Cells, Natural - microbiology; Killer Cells, Natural - pathology; Lyme Disease - genetics; Lyme Disease - immunology; Lyme Disease - microbiology; Lyme Disease - pathology; Macrophages, Peritoneal - immunology; Macrophages, Peritoneal - microbiology; Macrophages, Peritoneal - pathology; Mice; Mice, Inbred NOD; Mice, Knockout; Mice, SCID; Molecular Pathogenesis; Neutrophils - immunology; Neutrophils - microbiology; Neutrophils - pathology; T-Lymphocytes - immunology; T-Lymphocytes - microbiology; T-Lymphocytes - pathology
• ISSN: 0019-9567; 1098-5522
• DOI: 10.1128/IAI.01215-15

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.