The Lyme disease agent Borrelia burgdorferi is primarily transmitted to vertebrates by Ixodes ticks. The classical and alternative complement pathways are important in Borrelia eradication by the... Show moreThe Lyme disease agent Borrelia burgdorferi is primarily transmitted to vertebrates by Ixodes ticks. The classical and alternative complement pathways are important in Borrelia eradication by the vertebrate host. We recently identified a tick salivary protein, designated P8, which reduced complement-mediated killing of Borrelia. We now discover that P8 interferes with the human lectin complement cascade, resulting in impaired neutrophil phagocytosis and chemotaxis and diminished Borrelia lysis. Therefore, P8 was renamed the tick salivary lectin pathway inhibitor (TSLPI). TSLPI-silenced ticks, or ticks exposed to TSLPI-immune mice, were hampered in Borrelia transmission. Moreover, Borrelia acquisition and persistence in tick midguts was impaired in ticks feeding on TSLPI-immunized, B. burgdorferi-infected mice. Together, our findings suggest an essential role for the lectin complement cascade in Borrelia eradication and demonstrate how a vector-borne pathogen co-opts a vector protein to facilitate early mammalian infection and vector colonization. Show less
Schuijt, T.J.; Hovius, J.W.; Poll, T. van der; Dam, A.P. van; Fikrig, E. 2011
Lyme disease, or Lyme borreliosis, the most prevalent arthropod-borne disease in the Western world, is caused by spirochetes belonging to the Borrelia burgdorferi sensu lato group and is... Show moreLyme disease, or Lyme borreliosis, the most prevalent arthropod-borne disease in the Western world, is caused by spirochetes belonging to the Borrelia burgdorferi sensu lato group and is predominantly transmitted through lxodes ticks. There is currently no vaccine available to prevent Lyme borreliosis in humans. Borrelia outer membrane proteins are reviewed which have been investigated as vaccine candidates. In addition, several tick proteins are discussed, on which anti-tick vaccines have been based, or are interesting future candidates, to prevent transmission of the spirochete from the tick vector to the mammalian host. Finally, novel vaccination strategies to prevent Lyme borreliosis are proposed, based on multiple Borrelia antigens, tick antigens or a combination of both Borrelia as well as tick antigens. Show less
Repeated exposure of rabbits and other animals to ticks results in acquired resistance or immunity to subsequent tick bites and is partially elicited by antibodies directed against tick antigens.... Show moreRepeated exposure of rabbits and other animals to ticks results in acquired resistance or immunity to subsequent tick bites and is partially elicited by antibodies directed against tick antigens. In this study we demonstrate the utility of a yeast surface display approach to identify tick salivary antigens that react with tick-immune serum. We constructed an Ixodes scapularis nymphal salivary gland yeast surface display library and screened the library with nymph-immune rabbit sera and identified five salivary antigens. Four of these proteins, designated P8, P19, P23 and P32, had a predicted signal sequence. We generated recombinant (r) P8, P19 and P23 in a Drosophila expression system for functional and immunization studies. rP8 showed anti-complement activity and rP23 demonstrated anti-coagulant activity. Ixodes scapularis feeding was significantly impaired when nymphs were fed on rabbits immunized with a cocktail of rP8, rP19 and rP23, a hall mark of tick-immunity. These studies also suggest that these antigens may serve as potential vaccine candidates to thwart tick feeding. Show less
