葡萄牙里斯本大学医学院Maria M. Mota和Ângelo Ferreira Chora共同合作，近期取得重要工作进展。他们研究发现疟原虫感染的肝脏和血液阶段之间的相互作用通过γδ T细胞和IL-17促进应激红细胞生成决定了疟疾的严重程度。相关论文2023年2月17日在线发表于《免疫》杂志上。

据介绍，疟原虫在到达血液并感染红细胞之前在肝脏内复制。由于疟疾的临床表现仅出现在感染的血液阶段，因此存在一种看法，即肝脏感染不会影响疾病病理学。

通过建立肝脏和血液感染阶段分离的小鼠模型，研究人员发现两个阶段的信号整合决定了小鼠死亡率。这种二分法依赖于Vγ4⁺ γδT细胞的肝脏阶段依赖性激活。随后的血液阶段寄生虫负荷决定了它们的细胞因子分布图谱，其中低寄生虫负荷优先扩增产生IL-17的γδT细胞。IL-17驱动髓外红细胞生成和伴随的网状细胞增多，保护小鼠免受致命的实验性脑疟疾（ECM）。红系前体的过继转移可以将小鼠从ECM中解救出来。

总之，γδT细胞动力学模型表明，这种保护机制可能是在频繁暴露在疟疾中的个体中建立自然获得性疟疾免疫力的关键。

附：英文原文

Title: Interplay between liver and blood stages of Plasmodium infection dictates malaria severity via γδ T cells and IL-17-promoted stress erythropoiesis

Author: ngelo Ferreira Chora, Sofia Marques, Joana Lisboa Gonalves, Priscila Lima, Daniel Gomes da Costa, Daniel Fernandez-Ruiz, Maria Inês Marreiros, Pedro Ruivo, Tania Carvalho, Ruy M. Ribeiro, Karine Serre, William R. Heath, Bruno Silva-Santos, Ann T. Tate, Maria M. Mota

Issue&Volume: 2023-02-17

Abstract: Plasmodium replicates within the liver prior to reaching the bloodstream and infecting red blood cells. Because clinical manifestations of malaria only arise during the blood stage of infection, a perception exists that liver infection does not impact disease pathology. By developing a murine model where the liver and blood stages of infection are uncoupled, we showed that the integration of signals from both stages dictated mortality outcomes. This dichotomy relied on liver stage-dependent activation of Vγ4+ γδ T cells. Subsequent blood stage parasite loads dictated their cytokine profiles, where low parasite loads preferentially expanded IL-17-producing γδ T cells. IL-17 drove extra-medullary erythropoiesis and concomitant reticulocytosis, which protected mice from lethal experimental cerebral malaria (ECM). Adoptive transfer of erythroid precursors could rescue mice from ECM. Modeling of γδ T cell dynamics suggests that this protective mechanism may be key for the establishment of naturally acquired malaria immunity among frequently exposed individuals.

DOI: 10.1016/j.immuni.2023.01.031

Source: https://www.cell.com/immunity/fulltext/S1074-7613(23)00043-2