Forward genetics is an experimental approach in which gene mapping and positional cloning are used to elucidate the molecular mechanisms underlying phenotypic differences between two individuals for a given trait. This strategy has been highly successful for the study of inbred mouse strains that show differences in innate susceptibility to bacterial, parasitic, fungal, and viral infections. Over the past 20 years, these studies have led to the identification of a number of cell populations and critical biochemical pathways and proteins that are essential for the early detection of and response to invading pathogens. Strikingly, the macrophage is the point of convergence for many of these genetic studies. This has led to the identification of diverse pathways involved in extracellular and intracellular pathogen recognition, modification of the properties and content of phagosomes, transcriptional response, and signal transduction for activation of adaptive immune mechanisms. In models of viral infections, elegant genetic studies highlighted the pivotal role of natural killer cells in the detection and destruction of infected cells.

中文翻译：

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小鼠感染免疫的正向遗传解剖。

正向遗传学是一种实验方法，其中使用基因作图和定位克隆来阐明两个个体之间针对给定性状的表型差异背后的分子机制。这种策略在研究近交小鼠品系方面非常成功，这些品系对细菌、寄生虫、真菌和病毒感染的先天易感性存在差异。在过去的 20 年里，这些研究已经确定了许多细胞群和关键的生化途径和蛋白质，它们对于早期检测和应对入侵病原体至关重要。引人注目的是，巨噬细胞是许多这些遗传研究的汇聚点。这导致鉴定了涉及细胞外和细胞内病原体识别的多种途径，改变吞噬体的特性和含量、转录反应和信号转导以激活适应性免疫机制。在病毒感染模型中，优雅的遗传研究强调了自然杀伤细胞在检测和破坏受感染细胞中的关键作用。