Division of Immunology, Department of Molecular Microbiology and Immunology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
School of Tropical Medicine and Global Health, Nagasaki University, Nagasaki, Japan.
Parasite Immunol. 2021 Feb;43(2):e12763. doi: 10.1111/pim.12763. Epub 2020 Jun 17.
Human malarial infection occurs after an infectious Anopheles mosquito bites. Following the initial liver-stage infection, parasites transform into merozoites, infecting red blood cells (RBCs). Repeated RBC infection then occurs during the blood-stage infection, while patients experience various malarial symptoms. Protective immune responses are elicited by this systemic infection, but excessive responses are sometimes harmful for hosts. As parasites infect only RBCs and their immediate precursors during this stage, direct parasite-host interactions occur primarily in the environment surrounded by endothelial lining of blood vessels. The spleen is the major organ where the immune system encounters infected RBCs, causing immunological responses. Its tissue structure is markedly altered during malarial infection in mice and humans. Plasmodium falciparum parasites inside RBCs express proteins, such as PfEMP-1 and RIFIN, transported to the RBC surfaces in order to evade immunological attack by sequestering themselves in the peripheral vasculature avoiding spleen or by direct immune cell inhibition through inhibitory receptors. Host cell production of regulatory cytokines IL-10 and IL-27 limits excessive immune responses, avoiding tissue damage. The regulation of the protective and inhibitory immune responses through host-parasite interactions allows chronic Plasmodium infection. In this review, we discuss underlying interaction mechanisms relevant for developing effective strategies against malaria.
人类疟疾感染发生在感染性按蚊叮咬之后。在初始的肝期感染之后，寄生虫转化为裂殖子，感染红细胞（RBC）。在血期感染期间会反复发生 RBC 感染，而患者会出现各种疟疾症状。这种全身感染会引发保护性免疫反应，但过度的反应有时对宿主有害。由于寄生虫在这个阶段仅感染 RBC 及其直接前体，因此主要在血管内皮衬里包围的环境中发生寄生虫-宿主相互作用。脾脏是免疫系统遇到感染 RBC 的主要器官，会引发免疫反应。在小鼠和人类的疟疾感染中，其组织结构会发生明显改变。RBC 内的疟原虫表达蛋白质，如 PfEMP-1 和 RIFIN，这些蛋白质被运输到 RBC 表面，以通过将自身隔离在周围血管系统中避免脾脏或通过抑制性受体直接抑制免疫细胞来逃避免疫攻击。宿主细胞产生的调节性细胞因子 IL-10 和 IL-27 限制了过度的免疫反应，避免了组织损伤。通过宿主-寄生虫相互作用调节保护性和抑制性免疫反应，使得慢性疟原虫感染得以持续。在这篇综述中，我们讨论了相关的相互作用机制，这些机制对于开发有效的疟疾防治策略具有重要意义。
