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用利什曼原虫重组亲环素蛋白 1 免疫可对随后的寄生虫感染提供部分保护,并产生特异性记忆 T 细胞。

Immunization with the Leishmania infantum recombinant cyclophilin protein 1 confers partial protection to subsequent parasite infection and generates specific memory T cells.

机构信息

Unidade de Ensino e Investigação de Parasitologia Médica, Centro de Malária e Outras Doenças Tropicais, Instituto de Higiene e Medicina Tropical (IHMT), Universidade Nova de Lisboa, Rua da Junqueira 100, 1349-008 Lisboa, Portugal.

Unidade de Ensino e Investigação de Parasitologia Médica, Centro de Malária e Outras Doenças Tropicais, Instituto de Higiene e Medicina Tropical (IHMT), Universidade Nova de Lisboa, Rua da Junqueira 100, 1349-008 Lisboa, Portugal.

出版信息

Vaccine. 2014 Mar 5;32(11):1247-53. doi: 10.1016/j.vaccine.2014.01.024. Epub 2014 Jan 28.

Abstract

Control of zoonotic visceral leishmaniosis can be achieved using several available drugs. These drugs present high toxicity and require longer treatment regimens which complicate compliance to the treatment. Other control measures directed to the vector or the reservoirs are useful tools to restrain the spreading of this disease but the effects are transitory. A safe, affordable and efficient vaccine conferring long lasting immunity should be the most cost effective way of controlling zoonotic visceral leishmaniosis. The present study aims at characterizing a cyclophilin protein 1 of Leishmania infantum (LiCyP1) and investigating whether recombinant LiCyP1 (LirCyP1) is able to confer protection against infection by evaluating viable parasite load and the generation of specific CD4(+) and CD8(+) effector and central memory T cells in rodent model. LiCyP1 is present in the cytoplasm of L. infantum amastigotes and promastigotes. Immunization of BALB/c mice with LirCyP1 confers high protection to L. infantum infection, causing a marked reduction in parasite replication in the liver and spleen. Furthermore, helper and cytotoxic memory T cell subsets able to specifically recognize parasite antigens expanded in immunized and in challenged mice. CD4(+) T cell subpopulation of intermediate phenotype (CD62L(high)CD127(low)) of challenging mice also presented an accentuated expansion after the recall. This study demonstrated that LirCyP1 confers partial protection to L. infantum infection, promoting the generation of a desired long lasting immunity. LirCyP1 can be considered a potential candidate for the design of a vaccine against zoonotic visceral leishmaniosis.

摘要

控制动物源性内脏利什曼病可以使用几种现有药物。这些药物具有很高的毒性,需要更长的治疗方案,这使得治疗的依从性变得复杂。针对媒介或储存宿主的其他控制措施是限制这种疾病传播的有用工具,但效果是暂时的。一种安全、负担得起且有效的疫苗,可提供长期持久的免疫力,应该是控制动物源性内脏利什曼病的最具成本效益的方法。本研究旨在表征利什曼原虫(Leishmania infantum)的一种亲环蛋白 1(LiCyP1),并通过评估活寄生虫载量和特异性 CD4(+)和 CD8(+)效应和中央记忆 T 细胞的产生,研究重组 LiCyP1(LirCyP1)是否能够提供针对感染的保护,以评估重组 LiCyP1(LirCyP1)是否能够提供针对感染的保护。LiCyP1 存在于 L. infantum 无鞭毛体和前鞭毛体的细胞质中。用 LirCyP1 免疫 BALB/c 小鼠可提供对 L. infantum 感染的高度保护,导致肝脏和脾脏中寄生虫复制明显减少。此外,能够特异性识别寄生虫抗原的辅助和细胞毒性记忆 T 细胞亚群在免疫和挑战小鼠中扩增。挑战小鼠的中间表型(CD62L(high)CD127(low))CD4(+) T 细胞亚群在回忆后也表现出明显的扩增。这项研究表明,LirCyP1 可提供对 L. infantum 感染的部分保护,促进产生所需的长期免疫。LirCyP1 可以被认为是针对动物源性内脏利什曼病的疫苗设计的潜在候选物。

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