Wilson Sarah K, Knoll Laura J
Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, Madison, WI, 53706, USA.
Mol Microbiol. 2018 Jan;107(1):34-46. doi: 10.1111/mmi.13871. Epub 2017 Nov 23.
Emerging lipidomic technologies have enabled researchers to dissect the complex roles of phospholipases in lipid metabolism, cellular signaling and immune regulation. Host phospholipase products are involved in stimulating and resolving the inflammatory response to pathogens. While many pathogen-derived phospholipases also manipulate the immune response, they have recently been shown to be involved in lipid remodeling and scavenging during replication. Animal and plant hosts as well as many pathogens contain a family of patatin-like phospholipases, which have been shown to have phospholipase A activity. Proteins containing patatin-like phospholipase domains have been identified in protozoan parasites within the Apicomplexa phylum. These parasites are the causative agents of some of the most widespread human diseases. Malaria, caused by Plasmodium spp., kills nearly half a million people worldwide each year. Toxoplasma and Cryptosporidium infect millions of people each year with lethal consequences in immunocompromised populations. Parasite-derived patatin-like phospholipases are likely effective drug targets and progress in the tools available to the Apicomplexan field will allow for a closer look at the interplay of lipid metabolism and immune regulation during host infection.
新兴的脂质组学技术使研究人员能够剖析磷脂酶在脂质代谢、细胞信号传导和免疫调节中的复杂作用。宿主磷脂酶产物参与刺激和解决对病原体的炎症反应。虽然许多病原体衍生的磷脂酶也会操纵免疫反应,但最近发现它们在复制过程中参与脂质重塑和清除。动物和植物宿主以及许多病原体都含有一类类马铃薯Patatin磷脂酶,已证明它们具有磷脂酶A活性。在顶复门的原生动物寄生虫中已鉴定出含有类马铃薯Patatin磷脂酶结构域的蛋白质。这些寄生虫是一些最广泛传播的人类疾病的病原体。由疟原虫属引起的疟疾每年在全球导致近50万人死亡。弓形虫和隐孢子虫每年感染数百万人,对免疫功能低下人群造成致命后果。寄生虫衍生的类马铃薯Patatin磷脂酶可能是有效的药物靶点,顶复门领域现有工具的进展将有助于更深入地了解宿主感染期间脂质代谢和免疫调节的相互作用。