Harvard Medical School and Division of Gastroenterology, Children's Hospital Boston, Boston, MA 02115, USA.
Cell. 2012 Dec 7;151(6):1168-78. doi: 10.1016/j.cell.2012.11.011.
There are at least five families of microbe-detection receptors that function to detect and eradicate potentially infectious microorganisms that enter multicellular eukaryotes. While a multitude of proteins regulating innate immune signal transduction have already been defined, continuous genetic screening for regulators of innate immunity may not yield as significant insight into the operation of these pathways as was obtained in the past. This diminished return on experimental investment suggests that we are approaching the asymptote of genetics-only approaches to study innate immunity. In contrast, it remains unclear how known regulators of innate immunity interact within the infrastructure of mammalian cells to execute their signaling functions. In this Perspective, I first highlight the locations within mammalian cells that permit innate immune signal transduction and then offer a model whereby structurally distinct proteins can be grouped functionally through their ability to assemble platforms of regulators on the signaling organelles of the innate immune system.
至少有五类微生物检测受体家族，其功能是检测和消除可能进入多细胞真核生物的传染性微生物。虽然已经定义了许多调节先天免疫信号转导的蛋白质，但对先天免疫调节剂的连续遗传筛选可能不会像过去那样对这些途径的运作有重大的了解。这种实验投资回报的减少表明，我们正在接近仅通过遗传学方法研究先天免疫的渐近线。相比之下，目前尚不清楚先天免疫的已知调节剂如何在哺乳动物细胞的基础设施内相互作用以执行其信号转导功能。在本观点中，我首先强调了允许先天免疫信号转导的哺乳动物细胞内的位置，然后提出了一种模型，通过该模型，结构上不同的蛋白质可以通过其在先天免疫系统的信号细胞器上组装调节剂平台的能力来进行功能分组。
