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

Sebastian E. Carrasco, Bryan Troxell, Youyun Yang, Stephanie L. Brandt, Hongxia Li, George Sandusky, Keith W. Condon, C. Henrique Serezani, X. Yang

Research output: Contribution to journalArticle

32 Citations (Scopus)

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 IL2rγnull 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.

Original languageEnglish (US)
Pages (from-to)4848-4860
Number of pages13
JournalInfection and Immunity
Volume83
Issue number12
DOIs
StatePublished - 2015

Fingerprint

Borrelia burgdorferi
Spirochaetales
Phagocytosis
Membrane Proteins
Macrophages
Phagocytes
Infection
Inbred C3H Mouse
Peritoneal Macrophages
Immune Evasion
SCID Mice
Lyme Disease
Ticks
Green Fluorescent Proteins
Natural Killer Cells
Lipoproteins
OspC protein
Neutrophils
B-Lymphocytes
Joints

ASJC Scopus subject areas

  • Immunology
  • Microbiology
  • Parasitology
  • Infectious Diseases

Cite this

Outer surface protein OspC is an antiphagocytic factor that protects Borrelia burgdorferi from phagocytosis by macrophages. / Carrasco, Sebastian E.; Troxell, Bryan; Yang, Youyun; Brandt, Stephanie L.; Li, Hongxia; Sandusky, George; Condon, Keith W.; Serezani, C. Henrique; Yang, X.

In: Infection and Immunity, Vol. 83, No. 12, 2015, p. 4848-4860.

Research output: Contribution to journalArticle

Carrasco, Sebastian E. ; Troxell, Bryan ; Yang, Youyun ; Brandt, Stephanie L. ; Li, Hongxia ; Sandusky, George ; Condon, Keith W. ; Serezani, C. Henrique ; Yang, X. / Outer surface protein OspC is an antiphagocytic factor that protects Borrelia burgdorferi from phagocytosis by macrophages. In: Infection and Immunity. 2015 ; Vol. 83, No. 12. pp. 4848-4860.
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AU - Carrasco, Sebastian E.

AU - Troxell, Bryan

AU - Yang, Youyun

AU - Brandt, Stephanie L.

AU - Li, Hongxia

AU - Sandusky, George

AU - Condon, Keith W.

AU - Serezani, C. Henrique

AU - Yang, X.

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AB - 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 IL2rγnull 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.

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