MAINTENANCE OF PROTECTIVE IMMUNITY AGAINST MALARIA BY PERSISTENT HEPATIC PARASITES DERIVED FROM IRRADIATED SPOROZOITES

MAINTENANCE OF PROTECTIVE IMMUNITY AGAINST MALARIA BY PERSISTENT HEPATIC PARASITES DERIVED FROM IRRADIATED SPOROZOITES
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DOI:
10.1073/pnas.92.9.4066
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发表时间:
1995-04-25
影响因子:
11.1
通讯作者:
AZAD, AF
AZAD, AF
中科院分区:
综合性期刊1区
文献类型:
--
作者:
SCHELLER, LF;AZAD, AF

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用辐射致弱的疟疾子孢子免疫啮齿动物和人类,可提供红细胞期前特异的保护性免疫来攻击感染,这种免疫是针对肝脏内寄生虫的,涉及T细胞和干扰素γ,它们可以防止红外期的发展和随后的血液感染。本研究旨在探讨伯氏疟原虫子孢子免疫啮齿动物后如何获得保护性免疫。我们提出的证据表明,受辐射的寄生虫在免疫后在大鼠和小鼠的肝细胞中持续存在长达6个月。观察到寄生虫的持久性与保护性免疫的维持之间的关系。在应用化疗清除先前存在的肝脏寄生虫后,辐射子孢子免疫的大鼠的保护性免疫被取消。此外,在大鼠体内建立了对子孢子攻击的保护性免疫,这些结果表明辐射减毒的子孢子在体内产生持续的肝内阶段,是诱导和维持保护性免疫所必需的。
Immunization of rodents and humans with irradiation-attenuated malaria sporozoites confers preerythrocytic stage-specific protective immunity to challenge infection, This immunity is directed against intrahepatic parasites and involves T cells and interferon gamma, which prevent development of exoerythrocytic stages and subsequent blood infection. The present study was undertaken to determine how protective immunity is achieved after immunization of rodent hosts with irradiated Plasmodium berghei sporozoites. We present evidence that irradiated parasites persist in hepatocytes of rats and mice for up to 6 months after immunization. A relationship between the persistence of parasites and the maintenance of protective immunity was observed. Protective immunity was abrogated in irradiated-sporozoite-immunized rats following the application of chemotherapy to remove preexisting liver parasites. Additionally, protective immunity against sporozoite challenge was established in rats vaccinated with early and late hepatic stages of irradiated parasites, These results show that irradiation-attenuated sporozoites produce persistent intrahepatic stages in vivo necessary for the induction and maintenance of protective immunity.