A tick mannose-binding lectin inhibitor interferes with the vertebrate complement cascade to enhance transmission of the lyme disease agent

Tim J. Schuijt, Jeroen Coumou, Sukanya Narasimhan, Jianfeng Dai, Kathleen Deponte, Diana Wouters, Mieke Brouwer, Anneke Oei, Joris J. T. H. Roelofs, Alje P. van Dam, Tom van der Poll, Cornelis van't Veer, Joppe W. Hovius, Erol Fikrig

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132 Citations (Scopus)

Abstract

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 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
Original languageEnglish
Pages (from-to)136-146
JournalCELL Host & Microbe
Volume10
Issue number2
DOIs
Publication statusPublished - 2011

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