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利什曼原虫 eIF2α 激酶 LdeK1 的显性负突变体可引发宿主保护性免疫反应。

A Leishmania donovani dominant-negative mutant for eIF2α kinase LdeK1 elicits host-protective immune response.

机构信息

National Centre for Cell Science, Pune, India.

Genetics Laboratory, School of Health Sciences, Savitribai Phule Pune University, Pune, India.

出版信息

Parasite Immunol. 2020 Jan;42(1):e12678. doi: 10.1111/pim.12678. Epub 2019 Nov 6.

Abstract

Dominant-negative mutation of LdeK1 gene, an eIF2α kinase from Leishmania donovani, revealed its role in translation regulation in response to nutrient starvation earlier. However, whether the kinase influences the infectivity of the parasites which naturally encounters nutrient deprivation during its life cycle was interesting to investigate. Both in vitro and in vivo experiments resulted in decrease of the parasite burden in peritoneal macrophages and in splenic/ hepatic load, respectively. An insight into the immune response of mice infected with mutant parasite showed enhanced pro-inflammatory cytokines and nitric oxide levels but reduced T 2 and Treg population. The significantly reduced loss of infectivity of the parasites lacking a functional LdeK1 by modulating the immune response towards host protection makes it a potential vaccine candidate against Leishmaniasis.

摘要

LdeK1 基因是利什曼原虫中的一种 eIF2α 激酶,其显性负突变体早先被发现可调控翻译以响应营养饥饿。然而,这种激酶是否会影响寄生虫的感染力,这在寄生虫的生命周期中自然会遇到营养缺乏,这很值得研究。体内外实验分别导致腹腔巨噬细胞和脾/肝负荷中寄生虫载量减少。对感染突变寄生虫的小鼠的免疫反应进行深入研究表明,促炎细胞因子和一氧化氮水平增加,但 T2 和 Treg 群体减少。通过调节免疫反应以保护宿主,缺乏功能性 LdeK1 的寄生虫的感染力显著降低,这使其成为治疗利什曼病的潜在疫苗候选物。

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