Parasite load stemming from immunization route determines the duration of liver-stage immunity.
Parasite load stemming from immunization route determines the duration of liver-stage immunity.
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免疫途径产生的寄生虫负荷决定了肝期免疫的持续时间。
DOI：
10.1111/pim.12622
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发表时间：
2019
影响因子：
2.2
通讯作者：
Dalai,SaratK
中科院分区：
文献类型：
--
作者：
Patel,Hardik;Althubaiti,Nouf;Parmar,Rajesh;Yadav,Naveen;Joshi,Urja;Tyagi,RajeevK;Krzych,Urszula;Dalai,SaratK
辐射减毒疟原虫（RAS）免疫可诱导无菌和持久的保护性免疫。尽管有报道称，静脉（IV）途径的RAS免疫比皮内（ID）注射可诱导更高的免疫力，但其在维持无菌免疫中的作用尚不清楚。我们研究了伯氏疟原虫（Pb） RAS免疫小鼠的同源孢子子攻击途径是否会影响保护的寿命。经IV免疫Pb‐RAS的C57BL/6小鼠在IV/ID原代孢子虫攻击下具有100%的保护作用。相比之下，无论主要攻毒途径如何，ID免疫均产生80%的保护作用。有趣的是，发现初攻途径对无菌保护的维持有不同的影响。虽然IV Pb - RAS免疫小鼠在所有攻击中都保持保护作用，无论初次攻击的途径如何，但ID Pb - RAS免疫小鼠接受ID初次攻击后，在继发性IV攻击时变得寄生。值得注意的是，经Pb RAS ID‐免疫的小鼠在第二次和第三次IV攻击时的存活率分别为80%和50%。根据肝脏CD8+T细胞的表型差异，IV组CD8+T效应记忆细胞和常驻记忆细胞的百分比和数量均显著高于ID Pb RAS‐免疫小鼠。IFN‐γ‐产生特异性pbtrap130和MIP‐4‐Kb‐17的CD8+T细胞在IV小鼠中也明显高于ID小鼠。增强的T细胞生成和保护的寿命似乎取决于攻击期间的寄生虫负荷，当感染在次优CD8+T细胞反应下耐受时。
Immunization with radiation‐attenuatedPlasmodiumsporozoites (RAS) induces sterile and long‐lasting protective immunity. Although intravenous (IV) route of RAS immunization is reported to induce superior immunity compared to intradermal (ID) injection, its role in the maintenance of sterile immunity is yet to be understood. We investigated whether the route of homologous sporozoite challenge ofPlasmodium berghei(Pb) RAS‐immunized mice would influence the longevity of protection. C57BL/6 mice immunized with Pb‐RAS by IV were 100% protected upon primary IV/ID sporozoite challenge. In contrast, ID immunization resulted in 80% protection, regardless of primary challenge route. Interestingly, the route of primary challenge was found to bring difference in the maintenance of sterile protection. While IV Pb RAS‐immunized mice remained protected at all challenges regardless of the route of primary challenge, ID Pb‐RAS‐immunized mice receiving ID primary challenge became parasitaemic upon secondary IV challenge. Significantly, primary IV challenge of Pb RAS ID‐immunized mice resulted in 80% and 50% survival at secondary and tertiary challenges, respectively. According to phenotypically diverse liver CD8+T cells, the percentages and the numbers of both CD8+T effector memory and resident memory cells were significantly higher in IV than in ID Pb RAS‐immunized mice. IFN‐γ‐producing CD8+T cells specific to Pb TRAP130and MIP‐4‐Kb‐17 were also found significantly higher in IV mice than in ID mice. The enhanced T‐cell generation and the longevity of protection appear to be dependent on the parasite load during challenge when infection is tolerated under suboptimal CD8+T‐cell response.