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实验性恰加斯病。先前用朗氏锥虫接种过的Balb/c小鼠的天然免疫反应。I. 巨噬细胞显示免疫记忆:事实还是虚构?

Experimental Chagas disease. Innate immune response in Balb/c mice previously vaccinated with Trypanosoma rangeli. I. The macrophage shows immunological memory: Reality or fiction?

作者信息

Basso B, Marini V

机构信息

Department of Paediatrics, Neonatology Service, Medicine School, National Cordoba University, Argentina; National Co-ordination of Vector Control, Argentina.

Department of Immunology Medicine School, Catholic University of Cordoba, Argentina.

出版信息

Immunobiology. 2014 Apr;219(4):275-84. doi: 10.1016/j.imbio.2013.10.012. Epub 2013 Nov 8.

Abstract

Chagas' disease, caused by Trypanosoma cruzi, is a major vector borne health problem in Latin America and an emerging or re-emerging infectious disease in several countries. Immune response to T. cruzi infection is highly complex and involves many components, both regulators and effectors. Although different parasites have been shown to activate different mechanisms of innate immunity, T. cruzi is often able to survive and replicate in its host because they are well adapted to resisting host defences. An experimental model for vaccinating mice with Trypanosoma rangeli, a parasite closely related to T. cruzi, but nonpathogenic to humans, has been designed in our laboratory, showing protection against challenge with T. cruzi infection. The aim of this work was to analyze some mechanisms of the early innate immune response in T. rangeli vaccinated mice challenged with T. cruzi. For this purpose, some interactions were studied between T. cruzi and peritoneal macrophages of mice vaccinated with T. rangeli, infected or not with T. cruzi and the levels of some molecules or soluble mediators which could modify these interactions. The results in vaccinated animals showed a strong innate immune response, where the adherent cells of the vaccinated mice revealed important phagocytic activity, and some soluble mediator (Respiratory Burst: significantly increase, p ≤ 0.03; NO: the levels of vaccinated animals were lower than those of the control group; Arginasa: significantly increase, p ≤ 0.04). The results showed an important role in the early elimination of the parasites and their close relation with the absence of histological lesions that these animals present with regard to the only infected mice. This behaviour reveals that the macrophages act with some type of memory, recognizing the antigens to which they have previously been exposed, in mice were vaccinated with T. rangeli, which shares epitopes with T. cruzi.

摘要

恰加斯病由克氏锥虫引起,是拉丁美洲一个主要的媒介传播健康问题,并且在一些国家是一种新出现或再次出现的传染病。对克氏锥虫感染的免疫反应高度复杂,涉及许多成分,包括调节因子和效应因子。尽管已表明不同的寄生虫会激活不同的固有免疫机制,但克氏锥虫通常能够在其宿主中存活和繁殖,因为它们非常适应抵抗宿主防御。我们实验室设计了一种用与克氏锥虫密切相关但对人类无致病性的兰氏锥虫给小鼠接种疫苗的实验模型,结果显示该模型能抵御克氏锥虫感染的攻击。这项工作的目的是分析用兰氏锥虫接种疫苗的小鼠在受到克氏锥虫攻击时早期固有免疫反应的一些机制。为此,研究了克氏锥虫与用兰氏锥虫接种疫苗、感染或未感染克氏锥虫的小鼠腹膜巨噬细胞之间的一些相互作用,以及一些可能改变这些相互作用的分子或可溶性介质的水平。接种疫苗动物的结果显示出强烈的固有免疫反应,接种疫苗小鼠的贴壁细胞表现出重要的吞噬活性,并且一些可溶性介质(呼吸爆发:显著增加,p≤0.03;一氧化氮:接种疫苗动物的水平低于对照组;精氨酸酶:显著增加,p≤0.04)。结果表明在早期清除寄生虫方面其具有重要作用,并且与这些动物相对于仅感染小鼠而言不存在组织学病变密切相关。这种行为表明巨噬细胞以某种记忆方式发挥作用,识别它们先前接触过的抗原,在用与克氏锥虫有共同表位的兰氏锥虫接种疫苗的小鼠中就是如此。

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