Borrelia burgdorferi-pulsed dendritic cells induce a protective immune response against tick-transmitted spirochetes.
Borrelia burgdorferi-pulsed dendritic cells and epidermal cells were able to initiate the production of anti-outer surface protein A (OspA) antibody in vitro with normal T and B cells from either BALB/c or C3H/HeJ mice. Inhibition of anti-B. burgdorferi antibody production was observed after 3 days, but not after 2 days, of exposure of the antigen-presenting cells to tumor necrosis factor alpha +/- granulocyte-macrophage colony-stimulating factor. Furthermore, splenic dendritic cells pulsed in vitro with live B. burgdorferi spirochetes and then adoptively transferred into naive syngeneic mice mediated a protective immune response against tick-transmitted spirochetes. This protection appeared not to be due to killing of spirochetes in the feeding ticks, since ticks fed to repletion on B. burgdorferi-pulsed dendritic cell-sensitized mice still harbored live spirochetes. Western blot analysis of the sera collected from dendritic cell-sensitized mice demonstrated that the mice responded to a limited set of B. burgdorferi antigens, including OspA, -B, and -C compared to control groups that either had received unpulsed dendritic cells or were not treated. Finally, mice in the early stage of B. burgdorferi infection were able to develop anti-OspA antibody following injection with B. burgdorferi-pulsed dendritic cells. Our results demonstrate for the first time that adoptive transfer of B. burgdorferi-pulsed dendritic cells induces a protective immune response against tick-transmitted B. burgdorferi and stimulates the production of antibodies specific for a limited set of B. burgdorferi antigens in vivo.
Mbow
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ML
Division of Vector-Borne Infectious Diseases, National Center for Infectious Disease, Centers for Disease Control and Prevention, Fort Collins, Colorado 80522, USA.
Zeidner
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N
Panella
N
N
Titus
R G
RG
Piesman
J
J
D019264:Adoptive Transfer; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis*; D000954:Antigens, Surface / Q000276:immunology; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology; D001428:Bacterial Vaccines; D015748:Borrelia burgdorferi Group / Q000276:immunology*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000502:physiology*; D005260:Female; D018884:Ixodes / Q000382:microbiology*; D007801:Langerhans Cells / Q000502:physiology; D008074:Lipoproteins; D008193:Lyme Disease / Q000517:prevention & control / Q000635:transmission*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D000907:Antibodies, Bacterial; D000954:Antigens, Surface; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D008074:Lipoproteins; C072045:OspA protein; D014409:Tumor Necrosis Factor-alpha