Travassos Leonardo H, Carneiro Leticia A M, Girardin Stephen E, Boneca Ivo G, Lemos Ramon, Bozza Marcelo T, Domingues Regina C P, Coyle Anthony J, Bertin John, Philpott Dana J, Plotkowski Maria Cristina
Instituto de Microbiologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ Cep. 21.941 590, Brazil.
J Biol Chem. 2005 Nov 4;280(44):36714-8. doi: 10.1074/jbc.M501649200. Epub 2005 Sep 2.
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.
哺乳动物的固有免疫系统通过病原体识别受体识别病原体相关分子模式。Nod1最近被描述为一种胞质受体,可特异性检测革兰氏阴性菌肽聚糖中含二氨基庚二酸的胞壁肽。在本研究中,我们调查了Nod1在针对机会性病原体铜绿假单胞菌的固有免疫反应中的潜在作用。我们证明,Nod1可检测铜绿假单胞菌肽聚糖,导致核因子κB激活,并且在表达显性负性Nod1构建体的上皮细胞或感染铜绿假单胞菌的Nod1基因敲除小鼠的胚胎成纤维细胞中,这种活性会减弱。最后,我们证明,在感染早期感染铜绿假单胞菌的Nod1缺陷细胞中,细胞因子分泌动力学和细菌杀伤作用会发生改变。