Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, United States of America.
PLoS One. 2006 Dec 20;1(1):e77. doi: 10.1371/journal.pone.0000077.
In the past decade, Caenorhabditis elegans has been used to dissect several genetic pathways involved in immunity; however, little is known about transcription factors that regulate the expression of immune effectors. C. elegans does not appear to have a functional homolog of the key immune transcription factor NF-kappaB. Here we show that that the intestinal GATA transcription factor ELT-2 is required for both immunity to Salmonella enterica and expression of a C-type lectin gene, clec-67, which is expressed in the intestinal cells and is a good marker of S. enterica infection. We also found that ELT-2 is required for immunity to Pseudomonas aeruginosa, Enterococcus faecalis, and Cryptococcus neoformans. Lack of immune inhibition by DAF-2, which negatively regulates the FOXO transcription factor DAF-16, rescues the hypersusceptibility to pathogens phenotype of elt-2(RNAi) animals. Our results indicate that ELT-2 is part of a multi-pathogen defense pathway that regulates innate immunity independently of the DAF-2/DAF-16 signaling pathway.
在过去的十年中,秀丽隐杆线虫已被用于解析参与免疫的几个遗传途径;然而,对于调节免疫效应物表达的转录因子知之甚少。秀丽隐杆线虫似乎没有功能上类似于关键免疫转录因子 NF-κB 的同源物。在这里,我们表明肠道 GATA 转录因子 ELT-2 对于沙门氏菌和 C 型凝集素基因 clec-67 的表达均是必需的,该基因在肠道细胞中表达,是沙门氏菌感染的良好标志物。我们还发现 ELT-2 对于铜绿假单胞菌、粪肠球菌和新型隐球菌的免疫也是必需的。缺乏 DAF-2 对 FOXO 转录因子 DAF-16 的负调控,可挽救 elt-2(RNAi)动物对病原体的超敏反应表型。我们的结果表明,ELT-2 是多病原体防御途径的一部分,该途径独立于 DAF-2/DAF-16 信号通路调节先天免疫。