Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.
Mucosal Immunol. 2022 Jun;15(6):1224-1233. doi: 10.1038/s41385-022-00532-9. Epub 2022 Jun 22.
Helminths have evolved sophisticated immune regulating mechanisms to prevent rejection by their mammalian host. Our understanding of how the human immune system responds to these parasites remains poor compared to mouse models of infection and this limits our ability to develop vaccines as well as harness their unique properties as therapeutic strategies against inflammatory disorders. Here, we review how recent studies on human challenge infections, self-infected individuals, travelers, and endemic populations have improved our understanding of human type 2 immunity and its effects on the microbiome. The heterogeneity of responses between individuals and the limited access to tissue samples beyond the peripheral blood are challenges that limit human studies on helminths, but also provide opportunities to transform our understanding of human immunology. Organoids and single-cell sequencing are exciting new tools for immunological analysis that may aid this pursuit. Learning about the genetic and immunological basis of resistance, tolerance, and pathogenesis to helminth infections may thus uncover mechanisms that can be utilized for therapeutic purposes.
寄生虫进化出了复杂的免疫调节机制,以防止被其哺乳动物宿主排斥。与感染的小鼠模型相比,我们对人体免疫系统如何对这些寄生虫做出反应的理解仍然很差,这限制了我们开发疫苗以及利用它们作为治疗炎症性疾病的独特策略的能力。在这里,我们回顾了最近关于人体挑战感染、自身感染个体、旅行者和流行地区人群的研究如何提高我们对人类 2 型免疫及其对微生物组影响的理解。个体之间反应的异质性以及除外周血之外对组织样本的有限获取,是限制人体寄生虫研究的挑战,但也为我们转变对人类免疫学的理解提供了机会。类器官和单细胞测序是免疫分析的令人兴奋的新工具,可能有助于这一研究。了解对寄生虫感染的抗性、耐受性和发病机制的遗传和免疫学基础,可能会揭示可用于治疗目的的机制。