Sydney School of Veterinary Science, The University of Sydney, Faculty of Science, Sydney, NSW, Australia.
Sci Rep. 2022 Jun 11;12(1):9681. doi: 10.1038/s41598-022-13503-8.
Pathogenic mycobacteria including Mycobacterium avium subsp. paratuberculosis (MAP), the causative agent of Johne's disease, manipulate host macrophages to persist and cause disease. In mycobacterial infection, highly plastic macrophages, shift between inflammatory M1 and permissive M2 phenotypes which alter the disease outcome and allow bacteria to survive intracellularly. Here we examine the impact of MAP infection on polarised macrophages and how increased lipid availability alters macrophage phenotype and bacterial persistence. Further, we assess if host microRNA (miRNA) are sensitive to macrophage polarisation state and how MAP can drive their expression to overcome innate responses. Using in vitro MAP infection, we find that increasing lipid availability through supplementing culture media with exogenous lipid increases cellular nitric oxide production. Lipid-associated miRs -19a, -129, -24, and -24-3p are differentially expressed following macrophage polarisation and lipid supplementation and are further regulated during MAP infection. Collectively, our results highlight the importance of host lipid metabolism in MAP infection and demonstrate control of miRNA expression by MAP to favour intracellular persistence.
包括分枝杆菌属分枝杆菌亚种副结核分枝杆菌（MAP）在内的致病分枝杆菌是造成约氏病的病原体，它可以操纵宿主巨噬细胞持续存在并引发疾病。在分枝杆菌感染中，高度可塑性的巨噬细胞在炎症性 M1 和允许性 M2 表型之间转换，这改变了疾病的结果，并使细菌能够在细胞内存活。在这里，我们研究了 MAP 感染对极化巨噬细胞的影响，以及增加脂质可用性如何改变巨噬细胞表型和细菌的持久性。此外，我们评估了宿主 microRNA（miRNA）是否对巨噬细胞极化状态敏感，以及 MAP 如何驱动它们的表达以克服先天反应。通过体外 MAP 感染，我们发现通过在培养基中补充外源性脂质来增加脂质可用性会增加细胞内一氧化氮的产生。脂质相关的 miR-19a、-129、-24 和 -24-3p 在巨噬细胞极化和脂质补充后表达不同，并在 MAP 感染过程中进一步受到调节。总之，我们的研究结果强调了宿主脂质代谢在 MAP 感染中的重要性，并证明了 MAP 对 miRNA 表达的控制有利于细胞内持久性。
