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.

中文翻译：

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疟原虫血液阶段感染期间组织环境中的宿主-病原体相互作用

人疟疾感染发生在传染性按蚊之后蚊虫叮咬。在最初的肝阶段感染后，寄生虫转变为裂殖子，感染红细胞（RBC）。然后在血液阶段感染期间反复发生RBC感染，而患者会遇到各种疟疾症状。这种全身性感染可引起保护性免疫反应，但过度反应有时对宿主有害。在此阶段，由于寄生虫仅感染RBC及其直接前体，因此直接的寄生虫-宿主相互作用主要发生在被血管内皮衬里包围的环境中。脾脏是免疫系统遇到被感染的红细胞的主要器官，引起免疫反应。在小鼠和人类的疟疾感染过程中，其组织结构明显改变。恶性疟原虫RBC内部的寄生虫表达蛋白质，例如PfEMP-1和RIFIN，这些蛋白质被转运到RBC表面，以通过隔离自身在外周血管中避免脾脏或通过抑制性受体对免疫细胞的直接抑制来逃避免疫攻击。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可导致慢性疟原虫感染。在这篇综述中，我们讨论了与制定抗疟有效策略有关的潜在相互作用机制。