Document Detail


Cutting edge: a Toll-like receptor 2 polymorphism that is associated with lepromatous leprosy is unable to mediate mycobacterial signaling.
MedLine Citation:
PMID:  12646604     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Toll-like receptors (TLRs) are key mediators of the innate immune response to microbial pathogens. We investigated the role of TLRs in the recognition of Mycobacterium leprae and the significance of TLR2Arg(677)Trp, a recently discovered human polymorphism that is associated with lepromatous leprosy. In mice, TNF-alpha production in response to M. leprae was essentially absent in TLR2-deficient macrophages. Similarly, human TLR2 mediated M. leprae-dependent activation of NF-kappaB in transfected Chinese hamster ovary and human embryonic kidney 293 cells, with enhancement of this signaling in the presence of CD14. In contrast, activation of NF-kappaB by human TLR2Arg(677)Trp was abolished in response to M. leprae and Mycobacterium tuberculosis. The impaired function of this TLR2 variant provides a molecular mechanism for the poor cellular immune response associated with lepromatous leprosy and may have important implications for understanding the pathogenesis of other mycobacterial infections.
Authors:
Pierre-Yves Bochud; Thomas R Hawn; Alan Aderem
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  170     ISSN:  0022-1767     ISO Abbreviation:  J. Immunol.     Publication Date:  2003 Apr 
Date Detail:
Created Date:  2003-03-20     Completed Date:  2003-07-08     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3451-4     Citation Subset:  AIM; IM    
Affiliation:
Institute for Systems Biology, Seattle, WA 98103-8904, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Arginine / genetics
CHO Cells
Cell Line
Cricetinae
Humans
Immunity, Innate / genetics
Leprosy, Lepromatous / genetics*,  immunology*,  microbiology
Membrane Glycoproteins / deficiency*,  genetics*,  physiology
Mice
Mice, Inbred C57BL
Mice, Knockout
Mycobacterium leprae / immunology*
Mycobacterium tuberculosis / immunology
Polymorphism, Single Nucleotide / immunology*
Receptors, Cell Surface / deficiency*,  genetics*,  physiology
Signal Transduction / immunology*
Toll-Like Receptor 2
Toll-Like Receptors
Tryptophan / genetics
Grant Support
ID/Acronym/Agency:
AI25032/AI/NIAID NIH HHS; K08-AI49374/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Membrane Glycoproteins; 0/Receptors, Cell Surface; 0/TLR2 protein, human; 0/Toll-Like Receptor 2; 0/Toll-Like Receptors; 73-22-3/Tryptophan; 74-79-3/Arginine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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