Arthropod- and host-specific Borrelia burgdorferi bbk32 expression and the inhibition of spirochete transmission.
Antisera to BBK32 (a Borrelia burgdorferi fibronectin-binding protein) and BBK50, two Ags synthesized during infection, protect mice from experimental syringe-borne Lyme borreliosis. Therefore, B. burgdorferi bbk32 and bbk50 expression within Ixodes scapularis ticks and the murine host, and the effect of BBK32 and BBK50 antisera on spirochetes throughout the vector-host life cycle were investigated. bbk32 and bbk50 mRNA and protein were first detected within engorged ticks, demonstrating regulated expression within the vector. Then bbk32 expression increased in mice at the cutaneous site of inoculation. During disseminated murine infection, bbk32 and bbk50 were expressed in several murine tissues, and mRNA levels were greatest in the heart and spleen at 30 days. BBK32 antisera protected mice from tick-borne B. burgdorferi infection and spirochete numbers were reduced by 90% within nymphs that engorged on immunized mice. Moreover, 75% of these ticks did not retain spirochetes upon molting, and subsequent B. burgdorferi transmission by adult ticks was impaired. Larval acquisition of B. burgdorferi by I. scapularis was also inhibited by BBK32 antisera. These data demonstrate that bbk32 and bbk50 are expressed during tick engorgement and that BBK32 antisera can interfere with spirochete transmission at various stages of the vector-host life cycle. These studies provide insight into mechanisms of immunity to Lyme borreliosis and other vector-borne diseases.
Fikrig
E
E
Section of Rheumatology, Department of Internal Medicine, Section of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06520, USA.
Feng
W
W
Barthold
S W
SW
Telford
S R
SR
Flavell
R A
RA
D000818:Animals; D001096:Arachnid Vectors / Q000235:genetics / Q000276:immunology / Q000382:microbiology*; D001426:Bacterial Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D015748:Borrelia burgdorferi Group / Q000235:genetics / Q000254:growth & development* / Q000276:immunology*; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D006168:Guinea Pigs; D007106:Immune Sera / Q000008:administration & dosage; D007271:Injections, Intradermal; D018884:Ixodes / Q000235:genetics / Q000254:growth & development / Q000276:immunology* / Q000382:microbiology*; D007814:Larva / Q000254:growth & development / Q000276:immunology; D008193:Lyme Disease / Q000276:immunology* / Q000382:microbiology / Q000469:parasitology / Q000517:prevention & control*; D051379:Mice; D008809:Mice, Inbred C3H; D016513:Mice, SCID; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D001426:Bacterial Proteins; D007106:Immune Sera; D012333:RNA, Messenger; C106209:p35 antigen, Borrelia; C106210:p37 antigen, Borrelia