Wellcome Centre for Integrative Parasitology, Institute of Infection and Immunity, University of Glasgow, Glasgow, UK.
Immune Regulation Research Group, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.
Parasite Immunol. 2023 Dec;45(12):e12975. doi: 10.1111/pim.12975. Epub 2023 Feb 28.
During inflammation, haematopoietic stem cells (HSCs) in the bone marrow (BM) and periphery rapidly expand and preferentially differentiate into myeloid cells that mediate innate immune responses. HSCs can be directed into quiescence or differentiation by sensing alterations to the haematopoietic niche, including cytokines, chemokines, and pathogen-derived products. Most studies attempting to identify the mechanisms of haematopoiesis have focused on bacterial and viral infections. From intracellular protozoan infections to large multicellular worms, parasites are a global health burden and represent major immunological challenges that remain poorly defined in the context of haematopoiesis. Immune responses to parasites vary drastically, and parasites have developed sophisticated immunomodulatory mechanisms that allow development of chronic infections. Recent advances in imaging, genomic sequencing, and mouse models have shed new light on how parasites induce unique forms of emergency haematopoiesis. In addition, parasites can modify the haematopoiesis in the BM and periphery to improve their survival in the host. Parasites can also induce long-lasting modifications to HSCs, altering future immune responses to infection, inflammation or transplantation, a term sometimes referred to as central trained immunity. In this review, we highlight the current understanding of parasite-induced haematopoiesis and how parasites target this process to promote chronic infections.
在炎症期间,骨髓(BM)和外周血中的造血干细胞(HSCs)迅速扩增,并优先分化为介导先天免疫反应的髓系细胞。HSCs 可以通过感知造血龛位的变化,包括细胞因子、趋化因子和病原体衍生产物,被导向静止或分化。大多数试图确定造血机制的研究都集中在细菌和病毒感染上。从细胞内原生动物感染到大型多细胞蠕虫,寄生虫是全球健康负担,代表了在造血背景下仍未明确的主要免疫挑战。对寄生虫的免疫反应差异很大,寄生虫已经开发出复杂的免疫调节机制,允许慢性感染的发展。最近在成像、基因组测序和小鼠模型方面的进展,揭示了寄生虫如何诱导独特形式的紧急造血。此外,寄生虫可以改变 BM 和外周血中的造血,以提高其在宿主中的生存能力。寄生虫还可以诱导 HSCs 的长期改变,改变未来对感染、炎症或移植的免疫反应,这一术语有时被称为中央训练免疫。在这篇综述中,我们强调了目前对寄生虫诱导造血的理解,以及寄生虫如何针对这一过程来促进慢性感染。