Infectious diseases of farmed and wild animals pose a recurrent threat to food security and human health. The macrophage, a key component of the innate immune system, is the first line of defence against many infectious agents and plays a major role in shaping the adaptive immune response. However, this phagocyte is a target and host for many pathogens. Understanding the molecular basis of interactions between macrophages and pathogens is therefore crucial for the development of effective strategies to combat important infectious diseases. We explored how pluripotent stem cells (PSCs) can provide a limitless in vitro supply of genetically and experimentally tractable macrophages from livestock. Porcine and bovine PSC-derived macrophages (PSCdMs) exhibited molecular and functional characteristics of ex vivo primary macrophages. Pig PSCdMs were productively infected by Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) and African Swine Fever Virus (ASFV), two of the most economically important and devastating viruses in pig farming. Moreover, Pig PSCdMs were readily amenable to genetic modification by CRISPR/Cas9 gene editing applied in parental stem cells, or directly by lentiviral vector transduction. PSCs and differentiated derivatives therefore provide a useful and ethical experimental platform to investigate the genetic and molecular basis of host-pathogen interactions in livestock.

中文翻译：

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干细胞衍生的巨噬细胞作为研究家畜宿主-病原体相互作用的新平台

养殖和野生动物的传染病对粮食安全和人类健康构成反复威胁。巨噬细胞是先天免疫系统的关键组成部分，是抵御许多传染性病原体的第一道防线，在形成适应性免疫反应方面发挥着重要作用。然而，这种吞噬细胞是许多病原体的目标和宿主。因此，了解巨噬细胞和病原体之间相互作用的分子基础对于制定对抗重要传染病的有效策略至关重要。我们探索了多能干细胞 (PSC) 如何在体外提供无限的来自家畜的遗传和实验上易处理的巨噬细胞。猪和牛 PSC 衍生的巨噬细胞 (PSCdMs) 表现出的分子和功能特征离体原代巨噬细胞。猪 PSCdM 被猪生殖和呼吸综合征病毒 (PRRSV) 和非洲猪瘟病毒 (ASFV) 高效感染，这两种病毒是养猪业中最具经济意义和破坏性的病毒。此外，Pig PSCdM 易于通过应用于亲本干细胞的 CRISPR/Cas9 基因编辑或直接通过慢病毒载体转导进行遗传修饰。因此，PSC 和分化衍生物提供了一个有用且符合伦理的实验平台，用于研究牲畜中宿主-病原体相互作用的遗传和分子基础。