Your browser doesn't support javascript.
Enterohemorrhagic Escherichia coli Tir inhibits TAK1 activation and mediates immune evasion.
Emerg Microbes Infect; 8(1): 734-748, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31130074
ABSTRACT
Many pathogens infect hosts through various immune evasion strategies. However, the molecular mechanisms by which pathogen proteins modulate and evade the host immune response remain unclear. Enterohemorrhagic Escherichia coli (EHEC) is a pathological strain that can induce mitogen-activated protein (MAP) kinase (Erk, Jnk and p38 MAPK) and NF-κB pathway activation and proinflammatory cytokine production, which then causes diarrheal diseases such as hemorrhagic colitis and hemolytic uremic syndrome. Transforming growth factor ß-activated kinase-1 (TAK1) is a key regulator involved in distinct innate immune signalling pathways. Here we report that EHEC translocated intimin receptor (Tir) protein inhibits the expression of EHEC-induced proinflammatory cytokines by interacting with the host tyrosine phosphatase SHP-1, which is dependent on the phosphorylation of immunoreceptor tyrosine-based inhibition motifs (ITIMs). Mechanistically, the association of EHEC Tir with SHP-1 facilitated the recruitment of SHP-1 to TAK1 and inhibited TAK1 phosphorylation, which then negatively regulated K63-linked polyubiquitination of TAK1 and downstream signal transduction. Taken together, these results suggest that EHEC Tir negatively regulates proinflammatory responses by inhibiting the activation of TAK1, which is essential for immune evasion and could be a potential target for the treatment of bacterial infection.
Assuntos

Similares

MEDLINE

...
LILACS

LIS

Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: MEDLINE Assunto principal: Receptores de Superfície Celular / MAP Quinase Quinase Quinases / Proteínas de Escherichia coli / Fatores de Virulência / Infecções por Escherichia coli / Escherichia coli Êntero-Hemorrágica / Interações Hospedeiro-Patógeno / Evasão da Resposta Imune Limite: Animais / Humanos Idioma: Inglês Revista: Emerg Microbes Infect Ano de publicação: 2019 Tipo de documento: Artigo