RESUMO
The mammalian innate immune system recognizes pathogen-associated molecular patterns through pathogen recognition receptors. Nod1 has been described recently as a cytosolic receptor that detects specifically diaminopimelate-containing muropeptides from Gram-negative bacteria peptidoglycan. In the present study we investigated the potential role of Nod1 in the innate immune response against the opportunistic pathogen Pseudomonas aeruginosa. We demonstrate that Nod1 detects the P. aeruginosa peptidoglycan leading to NF-kappaB activation and that this activity is diminished in epithelial cells expressing a dominant-negative Nod1 construct or in mouse embryonic fibroblasts from Nod1 knock-out mice infected with P. aeruginosa. Finally, we demonstrate that the cytokine secretion kinetics and bacterial killing are altered in Nod1-deficient cells infected with P. aeruginosa in the early stages of infection.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/fisiologia , Apoptose , Peptidoglicano/imunologia , Infecções por Pseudomonas/imunologia , Pseudomonas aeruginosa/patogenicidade , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Citocinas/metabolismo , Células Epiteliais/citologia , Células Epiteliais/imunologia , Células Epiteliais/metabolismo , Genes Dominantes , Humanos , Imunidade Inata , Cinética , Camundongos , Camundongos Knockout/microbiologia , NF-kappa B/metabolismo , Proteína Adaptadora de Sinalização NOD1 , Infecções por Pseudomonas/metabolismoRESUMO
Nod1 and Nod2 are cytosolic proteins involved in intracellular recognition of microbes and their products. Recently, it was shown that these proteins recognize different moieties of bacterial peptidoglycan (PGN) mediating non-specific pathogen resistance and possibly generating signals for the adaptive immune response. Moreover, mutations in the gene encoding Nod2 are associated with increased susceptibility to chronic inflammatory disorders.