The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5 Fumitaka...
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Transcript of The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5 Fumitaka...
![Page 1: The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5 Fumitaka Hayashi*, Kelly D. Smith²³, Adrian Ozinsky², Thomas R. Hawn²§,](https://reader036.fdocuments.in/reader036/viewer/2022062522/5706386e1a28abb8239067fa/html5/thumbnails/1.jpg)
The innate immune response tobacterial flagellin is mediated
by Toll-like receptor 5Fumitaka Hayashi*, Kelly D. Smith²³, Adrian Ozinsky²,
Thomas R. Hawn²§, Eugene C. Yi², David R. Goodlett², Jimmy K. Eng²,Shizuo Akirak, David M. Underhill² & Alan Aderem²
Bacterial flagellins: mediators ofpathogenicity and host immuneresponses in mucosaHugo Cruz Ramos1, Martin Rumbo2 and Jean-Claude Sirard1
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Flagelos Bacterianos
Contribuem para a patogenia bacteriana através de:
Quimiotaxia Adesão Invasão a superfícies do hospedeiro
1- Motilidade associada a quimiotaxia2- Adesão ao muco ou a superfície celular3- Fatores de virulência exportados pelo sistema secretor flagelar envenenam e sequestram maquinaria das células epiteliais4- Invasão durante a infecção
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Organização do Flagelo e Flagelina
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Resposta Imune
O reconhecimento se dá por receptores Toll-Like do tipo 5 por motivos estruturais altamente conservados chamados de MAMPS/PAMPS (pathogen-associated molecular patterns) encontrados nas flagelinas
A ativação do receptor recruta proteínas adaptadoras MyD88 que , por meio de uma cascata molecular intracelular, sinalizam NFkB e MAPK, levando a expressão de mediadores inflamatórios
TLR5 é um receptor encontrado em monócitos, neutrófilos, células dendríticas e células epiteliais
Em células epiteliais, as flagelinas de algumas bactérias estimulam a secreção de IL-8 que é um potente quimiotáxico para o recrutamento de macrófagos e neutrófilos para a região de injúria
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Sinalização de Mediadores Inflamatórios
Receptores família TRL:
TLR 4 LPS TLR2 Lipopeptídeos TLR2-TLR6 Peptidoglicanos TLR5 Flagelinas
A sinalização por TLR5 se dá por monômeros de flagelina e não o flagelo filamentoso em si
TLR5 reconhece flagelinas tanto de Gram-negativa quanto Gram-positiva
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Atividade do Receptor
Proteínaluciferase associada a TNFproduzido pela sinalização de NF-kB
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Resposta dos Receptores
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Atividade da NF-kB luciferase mediada por TLR5 em células CHO
Teste da atividade das bandas purificadas
Análise ao estímulo de TLR5 por SDS-Page
Análise ao estímulo de TLR5 por SDS-Page
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Sequências Referentes a Flagelina
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Expressão e Repressão da Flagelina
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Indução da produção de IL-6 é dependente da molécula adaptadora MyD88
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Considerações Finais
A flagelina estimula a defesa inata do hospedeiro, levando as células a iniciar um processo inflamatório
O reconhecimento flagelina-receptor é específico
As evidências demonstram que TLR5 tem um reconhecimento padrão para flagelinas