title: A tick mannose-binding lectin inhibitor interferes with the vertebrate complement cascade to enhance transmission of the lyme disease agent.
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.
authors.affiliation: Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06420, USA. t.j.schuijt@amc.uva.nl
authors.forename: Tim J
authors.initials: TJ
authors.lastname: Schuijt
authors.forename: Jeroen
authors.initials: J
authors.lastname: Coumou
authors.forename: Sukanya
authors.initials: S
authors.lastname: Narasimhan
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Dai
authors.forename: Kathleen
authors.initials: K
authors.lastname: Deponte
authors.forename: Diana
authors.initials: D
authors.lastname: Wouters
authors.forename: Mieke
authors.initials: M
authors.lastname: Brouwer
authors.forename: Anneke
authors.initials: A
authors.lastname: Oei
authors.forename: Joris J T H
authors.initials: JJ
authors.lastname: Roelofs
authors.forename: Alje P
authors.initials: AP
authors.lastname: van Dam
authors.forename: Tom
authors.initials: T
authors.lastname: van der Poll
authors.forename: Cornelis
authors.initials: C
authors.lastname: Van't Veer
authors.forename: Joppe W
authors.initials: JW
authors.lastname: Hovius
authors.forename: Erol
authors.initials: E
authors.lastname: Fikrig
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D025065:Borrelia burgdorferi / Q000276:immunology / Q000472:pathogenicity*; D054443:Cell Migration Assays; D003001:Cloning, Molecular; D015938:Complement Membrane Attack Complex / Q000276:immunology; D037582:Complement Pathway, Mannose-Binding Lectin; D005260:Female; D020868:Gene Silencing; D006461:Hemolysis / Q000276:immunology; D006801:Humans; D007116:Immunization, Passive; D016233:Immunotherapy, Active; D019476:Insect Proteins / Q000276:immunology* / Q000494:pharmacology; D018884:Ixodes / Q000382:microbiology*; D007814:Larva / Q000382:microbiology; D008193:Lyme Disease / Q000276:immunology / Q000382:microbiology / Q000635:transmission*; D051379:Mice; D008809:Mice, Inbred C3H; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology; D009758:Nymph / Q000382:microbiology; D010587:Phagocytosis; D011817:Rabbits; D011994:Recombinant Proteins / Q000276:immunology / Q000494:pharmacology; D012463:Saliva / Q000276:immunology / Q000382:microbiology; D012471:Salivary Proteins and Peptides / Q000276:immunology / Q000494:pharmacology; D016415:Sequence Alignment
chemical_list: D015938:Complement Membrane Attack Complex; D019476:Insect Proteins; D011994:Recombinant Proteins; D012471:Salivary Proteins and Peptides