Department of Medical Microbiology, Radboudumc, The Netherlands.
Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.
Trends Parasitol. 2022 Nov;38(11):962-974. doi: 10.1016/j.pt.2022.08.013. Epub 2022 Sep 8.
During its life cycle, Plasmodium, the malaria parasite, is exposed to the human and mosquito complement systems. Early experiments demonstrated that activation of complement can pose a serious threat to parasites, but recent studies revealed complement-evasion mechanisms important for parasite survival. Blood-stage parasites and gametes recruit regulators to neutralize human complement activation, while ookinetes inhibit mosquito complement by disrupting epithelial nitration in response to midgut invasion. Here we provide an in-depth overview of the evasion mechanisms currently known and speculate on the existence of others not yet identified. Finally, we discuss how these mechanisms could provide novel targets for urgently needed malaria vaccines and therapeutics.
在生命周期中,疟原虫(疟疾寄生虫)会暴露于人体和蚊子的补体系统中。早期实验表明,补体的激活可能对寄生虫构成严重威胁,但最近的研究揭示了寄生虫生存所必需的补体逃避机制。血期寄生虫和配子通过招募调节剂来中和人体补体的激活,而子孢子通过破坏对肠道入侵的响应中的上皮硝化来抑制蚊子补体。在这里,我们提供了目前已知的逃避机制的深入概述,并推测了其他尚未确定的逃避机制的存在。最后,我们讨论了这些机制如何为急需的疟疾疫苗和疗法提供新的靶点。