Plasmodium vivax causes approximately 100 million clinical malaria cases yearly^1,2. The basis of protective immunity is poorly understood and thought to be mediated by antibodies^3,4. Cytotoxic CD8⁺ T cells protect against other intracellular parasites by detecting parasite peptides presented by human leukocyte antigen class I on host cells. Cytotoxic CD8⁺ T cells kill parasite-infected mammalian cells and intracellular parasites by releasing their cytotoxic granules^5,6. Perforin delivers the antimicrobial peptide granulysin and death-inducing granzymes into the host cell, and granulysin then delivers granzymes into the parasite. Cytotoxic CD8⁺ T cells were thought to have no role against Plasmodium spp. blood stages because red blood cells generally do not express human leukocyte antigen class I⁷. However, P. vivax infects reticulocytes that retain the protein translation machinery. Here we show that P. vivax-infected reticulocytes express human leukocyte antigen class I. Infected patient circulating CD8⁺ T cells highly express cytotoxic proteins and recognize and form immunological synapses with P. vivax-infected reticulocytes in a human leukocyte antigen-dependent manner, releasing their cytotoxic granules to kill both host cell and intracellular parasite, preventing reinvasion. P. vivax-infected reticulocytes and parasite killing is perforin independent, but depends on granulysin, which generally efficiently forms pores only in microbial membranes⁸. We find that P. vivax depletes cholesterol from the P. vivax-infected reticulocyte cell membrane, rendering it granulysin-susceptible. This unexpected T cell defense might be mobilized to improve P. vivax vaccine efficacy.

中文翻译：

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细胞毒性CD8 + T细胞识别并杀死间日疟原虫感染的网织红细胞。

间日疟原虫每年导致大约1亿例临床疟疾病例^1,2。保护性免疫的基础了解甚少，并认为是由抗体^3,4介导的。细胞毒性CD8 ⁺ T细胞通过检测宿主细胞上由I类人白细胞抗原呈递的寄生虫肽来防御其他细胞内寄生虫。细胞毒性的CD8 ⁺ T细胞通过释放其细胞毒性颗粒^5,6杀死被寄生虫感染的哺乳动物细胞和细胞内的寄生虫。穿孔素将抗微生物肽颗粒溶素和诱导死亡的颗粒酶传递到宿主细胞中，然后颗粒溶素将颗粒酶传递到寄生虫中。细胞毒性CD8 ⁺T细胞被认为对疟原虫没有作用。血液阶段，因为红细胞通常不表达人类白细胞抗原I ⁷类。但是，间日疟原虫感染保留了蛋白质翻译机制的网状细胞。在这里，我们显示间日疟原虫感染的网状细胞表达人类白细胞抗原I类。感染的患者循环CD8 ⁺T细胞高度表达细胞毒性蛋白，并以人白细胞抗原依赖性的方式识别间日疟原虫感染的网状细胞并与之形成免疫突触，释放其细胞毒性颗粒以杀死宿主细胞和细胞内寄生虫，从而防止再次入侵。间日疟原虫感染的网状细胞和寄生虫杀伤是穿孔素独立的，但取决于颗粒溶素，通常通常仅在微生物膜^8中有效地形成孔。我们发现间日疟原虫耗尽了间日疟原虫感染的网状红细胞细胞膜中的胆固醇，使其对颗粒溶素敏感。这种意想不到的T细胞防御可能会动员起来，以提高间日疟原虫疫苗的效力。