| A tick mannose-binding lectin inhibitor interferes with the vertebrate complement cascade to enhance transmission of the lyme disease agent. | |
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MedLine Citation:
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PMID: 21843870 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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 |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Cell host & microbe Volume: 10 ISSN: 1934-6069 ISO Abbreviation: Cell Host Microbe Publication Date: 2011 Aug |
Date Detail:
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Created Date: 2011-08-16 Completed Date: 2011-12-15 Revised Date: 2012-02-21 |
Medline Journal Info:
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Nlm Unique ID: 101302316 Medline TA: Cell Host Microbe Country: United States |
Other Details:
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Languages: eng Pagination: 136-46 Citation Subset: IM |
Copyright Information:
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Copyright © 2011 Elsevier Inc. All rights reserved. |
Affiliation:
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Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06420, USA. t.j.schuijt@amc.uva.nl |
| Data Bank Information | |
Bank Name/Acc. No.:
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GENBANK/AEE89466 |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Sequence Animals Borrelia burgdorferi / immunology, pathogenicity* Cell Migration Assays Cloning, Molecular Complement Membrane Attack Complex / immunology Complement Pathway, Mannose-Binding Lectin* Female Gene Silencing Hemolysis / immunology Humans Immunization, Passive Immunotherapy, Active Insect Proteins / immunology*, pharmacology Ixodes / microbiology* Larva / microbiology Lyme Disease / immunology, microbiology, transmission* Mice Mice, Inbred C3H Molecular Sequence Data Neutrophils / drug effects, immunology Nymph / microbiology Phagocytosis Rabbits Recombinant Proteins / immunology, pharmacology Saliva / immunology, microbiology Salivary Proteins and Peptides / immunology, pharmacology Sequence Alignment |
| Grant Support | |
ID/Acronym/Agency:
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32947//PHS HHS; 41440//PHS HHS; 49200//PHS HHS; R01 AI032947-20/AI/NIAID NIH HHS; R37 AI049200-12/AI/NIAID NIH HHS; //Howard Hughes Medical Institute |
| Chemical | |
Reg. No./Substance:
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0/Complement Membrane Attack Complex; 0/Insect Proteins; 0/Recombinant Proteins; 0/Salivary Proteins and Peptides |
| Comments/Corrections | |
Comment In:
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Cell Host Microbe. 2011 Aug 18;10(2):95-6
[PMID:
21843866
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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