Identification of innate immunity genes and pathways using a comparative genomics approach
Identification of innate immunity genes and pathways using a comparative genomics approach
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DOI：
10.1073/pnas.0802405105
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发表时间：
2008-05-13
影响因子：
11.1
通讯作者：
Schwartz, David A.
中科院分区：
文献类型：
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作者：
Alper, Scott;Laws, Rebecca;Schwartz, David A.
为了揭示先天免疫的调节因子，我们使用RNAi测定来监测秀丽隐杆线虫和小鼠巨噬细胞中基因被抑制时的免疫应答。在小鼠巨噬细胞中验证了改变线虫先天免疫应答的基因，发现了11个调节两个系统中先天免疫应答的基因，并随后鉴定了在先天免疫调节中具有保守作用的蛋白质相互作用网络。我们证实了这11个基因中的4个在使用可用的突变体在线虫中的抗菌基因调控中的作用。这些基因中的几个（acy-1，tub-2和tbc-1）也调节对病原体铜绿假单胞菌的易感性。这些基因可能对理解宿主防御至关重要，并代表了感染性和免疫性疾病的潜在治疗靶点。
To reveal regulators of innate immunity, we used RNAi assays to monitor the immune response when genes are inhibited in Caenorhabditis elegans and mouse macrophages. Genes that altered innate immune responsiveness in C elegans were validated in murine macrophages, resulting in the discovery of 11 genes that regulate the innate immune response in both systems and the subsequent identification of a protein interaction network with a conserved role in innate immunity regulation. We confirmed the role of four of these 11 genes in antimicrobial gene regulation using available mutants in C elegans. Several of these genes (acy-1, tub-2, and tbc-1) also regulate susceptibility to the pathogen Pseudomonas aeruginosa. These genes may prove critical to understanding host defense and represent potential therapeutic targets for infectious and immunological diseases.