title: An Ixodes ricinus Tick Salivary Lectin Pathway Inhibitor Protects Borrelia burgdorferi sensu lato from Human Complement.
abstract: BACKGROUND
  We previously identified tick salivary lectin pathway inhibitor (TSLPI) in Ixodes scapularis, a vector for Borrelia burgdorferi sensu stricto (s.s.) in North America. TSLPI is a salivary protein facilitating B. burgdorferi s.s. transmission and acquisition by inhibiting the host lectin complement pathway through interference with mannose binding lectin (MBL) activity. Since Ixodes ricinus is the predominant vector for Lyme borreliosis in Europe and transmits several complement sensitive B. burgdorferi sensu lato (s.l.) strains, we aimed to identify, describe, and characterize the I. ricinus ortholog of TSLPI.
  
  
  METHODS
  We performed (q)PCRs on I. ricinus salivary gland cDNA to identify a TSLPI ortholog. Next, we generated recombinant (r)TSLPI in a Drosophila expression system and examined inhibition of the MBL complement pathway and complement-mediated killing of B. burgdorferi s.l. in vitro.
  
  
  RESULTS
  We identified a TSLPI ortholog in I. ricinus salivary glands with 93% homology at the RNA and 89% at the protein level compared to I. scapularis TSLPI, which was upregulated during tick feeding. In silico analysis revealed that TSLPI appears to be part of a larger family of Ixodes salivary proteins among which I. persulcatus basic tail salivary proteins and I. scapularis TSLPI and Salp14. I. ricinus rTSLPI inhibited the MBL complement pathway and protected B. burgdorferi s.s. and Borrelia garinii from complement-mediated killing.
  
  
  CONCLUSIONS
  We have identified a TSLPI ortholog, which protects B. burgdorferi s.l. from complement-mediated killing in I. ricinus, the major vector for tick-borne diseases in Europe.
authors.affiliation: 1 Center for Experimental and Molecular Medicine, Academic Medical Center , Amsterdam, the Netherlands .
authors.forename: Alex
authors.initials: A
authors.lastname: Wagemakers
authors.affiliation: 1 Center for Experimental and Molecular Medicine, Academic Medical Center , Amsterdam, the Netherlands .
authors.forename: Jeroen
authors.initials: J
authors.lastname: Coumou
authors.affiliation: 1 Center for Experimental and Molecular Medicine, Academic Medical Center , Amsterdam, the Netherlands .
authors.forename: Tim J
authors.initials: TJ
authors.lastname: Schuijt
authors.affiliation: 2 Department of Medical Microbiology, Academic Medical Center , Amsterdam, the Netherlands .
authors.forename: Anneke
authors.initials: A
authors.lastname: Oei
authors.affiliation: 3 Institute of Parasitology and Tropical Veterinary Medicine , Berlin, Germany .
authors.forename: Ard M
authors.initials: AM
authors.lastname: Nijhof
authors.affiliation: 1 Center for Experimental and Molecular Medicine, Academic Medical Center , Amsterdam, the Netherlands .
authors.forename: Cornelis
authors.initials: C
authors.lastname: van 't Veer
authors.affiliation: 1 Center for Experimental and Molecular Medicine, Academic Medical Center , Amsterdam, the Netherlands .
authors.forename: Tom
authors.initials: T
authors.lastname: van der Poll
authors.affiliation: 1 Center for Experimental and Molecular Medicine, Academic Medical Center , Amsterdam, the Netherlands .
authors.forename: Adriaan D
authors.initials: AD
authors.lastname: Bins
authors.affiliation: 1 Center for Experimental and Molecular Medicine, Academic Medical Center , Amsterdam, the Netherlands .
authors.forename: Joppe W R
authors.initials: JW
authors.lastname: Hovius
mesh_terms: D000818:Animals; D001096:Arachnid Vectors / Q000378:metabolism / Q000382:microbiology; D060829:Arthropod Proteins / Q000096:biosynthesis*; D015748:Borrelia burgdorferi Group / Q000502:physiology*; D037582:Complement Pathway, Mannose-Binding Lectin; D006801:Humans; D018884:Ixodes / Q000235:genetics / Q000378:metabolism* / Q000382:microbiology; D008193:Lyme Disease / Q000276:immunology / Q000378:metabolism / Q000635:transmission; D012469:Salivary Glands / Q000378:metabolism* / Q000382:microbiology; D012471:Salivary Proteins and Peptides / Q000096:biosynthesis*
chemical_list: D060829:Arthropod Proteins; D012471:Salivary Proteins and Peptides
keywords: Borrelia burgdorferi; Immunology; Ixodes