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| Id: | 18953
| | Autor: | Bochud, Pierre-Yves; Hawn, Thomas R; Aderem, Alan
| | Título: | Cutting edge: a toll-like receptor 2 polymorphism that is associated with lepromatous leprosy is unable to mediate mycobacterial signaling
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| | Fonte: | s.l; s.n; 2003. 4 p. graf.
| | Resumo: | 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. (AU).
| | Descritores: | CELULAS CHO
LINHAGEM CELULAR
IMUNIDADE NATURAL/genet
ARGININA/genet
HANSENIASE VIRCHOWIANA/genet
HANSENIASE VIRCHOWIANA/imunol
HANSENIASE VIRCHOWIANA/microbiol
GLICOPROTEINAS DE MEMBRANA/defic
GLICOPROTEINAS DE MEMBRANA/genet
GLICOPROTEINAS DE MEMBRANA/fisiol
CAMUNDONGOS ENDOGÂMICOS C57BL
CAMUNDONGOS KNOCKOUT
MYCOBACTERIUM LEPRAE/imunol
MYCOBACTERIUM TUBERCULOSIS/imunol
POLIMORFISMO DE UM UNICO NUCLEOTIDIO/imunol
TRANSDUCAO DE SINAL/imunol
TRIPTOFANO/genet
RECEPTORES DA SUPERFICIE CELULAR/defic
RECEPTORES DA SUPERFICIE CELULAR/genet
RECEPTORES DA SUPERFICIE CELULAR/fisiol
| | Limites: | HUMANO
ANIMAL
HAMSTERS
CAMUNDONGOS
SUPPORT, NON-U.S. GOV'T
SUPPORT, U.S. GOV'T, P.H.S.
| | Meio Eletrônico: | - .
| | Localização: | BR191.1; 09085/s |
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