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重组肺炎军团菌肽聚糖相关脂蛋白(rPAL)蛋白在 BALB/c 小鼠模型中诱导保护性免疫。

Induction of protective immunity by recombinant peptidoglycan associated lipoprotein (rPAL) protein of Legionella pneumophila in a BALB/c mouse model.

机构信息

Department of Bacteriology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

Department of Microbiology and Virology, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran.

出版信息

Microb Pathog. 2019 Mar;128:100-105. doi: 10.1016/j.micpath.2018.12.014. Epub 2018 Dec 11.

Abstract

Legionella pneumophila causes a severe form of pneumonia known as Legionnaires' disease especially in patients with impaired cellular immune response. In order to prevent the disease, immunogenicity and the level of the induction of protective immunity from the recombinant peptidoglycan-associated lipoprotein (rPAL) against Legionella pneumophila in BALB/c mice was examined. Mice immunized with (rPAL) rapidly increased an antibody response in serum and also displayed a strong activation of both innate and adaptive cell-mediated immunity as determined by antigen-specific splenocyte proliferation, an early production of pro-inflammatory cytokines in the serum and in the splenocyte cultures. Infection with a primary sublethal does of Legionella pneumophila serogroup 1, strain paris, caused resistance to a lethal challenge infection in the animals with 100% survival rate. However, mice treated with rPAL survived with 60% rate in 10 days after a lethal i.v challenge with L. pneumophila. All of the control animals receiving PBS died within 24 h. The present study indicates that recombinant protein PAL of Legionella pneumophila is strongly immunogenic and capable to elicit early innate and adaptive immune responses and lasting immunity against a lethal dose of Legionella pneumophila challenge. Antigenic characterization and immune protection of recombinant protein PAL would be of considerable value in comprehension the immune-pathogenesis of the disease and in development possible vaccine against the Legionella.

摘要

嗜肺军团菌可引起一种严重的肺炎,称为军团病,尤其是在细胞免疫反应受损的患者中。为了预防这种疾病,研究了重组肽聚糖相关脂蛋白(rPAL)对嗜肺军团菌在 BALB/c 小鼠中的免疫原性和诱导保护性免疫的水平。用(rPAL)免疫的小鼠在血清中迅速增加了抗体反应,并且还表现出固有和适应性细胞介导免疫的强烈激活,这是通过抗原特异性脾细胞增殖、血清和脾细胞培养中早期产生促炎细胞因子来确定的。感染低致死剂量的嗜肺军团菌血清群 1 菌株巴黎,导致动物的致死性挑战感染具有 100%的存活率。然而,用 rPAL 治疗的小鼠在经静脉内给予致死剂量的嗜肺军团菌后 10 天内的存活率为 60%。所有接受 PBS 的对照动物在 24 小时内死亡。本研究表明,嗜肺军团菌的重组蛋白 PAL 具有很强的免疫原性,能够引发早期的固有和适应性免疫反应,并对致死剂量的嗜肺军团菌挑战产生持久的免疫力。重组蛋白 PAL 的抗原特征和免疫保护对于理解疾病的免疫发病机制以及开发针对军团菌的可能疫苗具有重要价值。

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