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用从蝙蝠中分离出的一种类似于克氏锥虫的株系免疫小鼠:预测嗜酸性粒细胞参与组织损伤的因素。

Immunization of mice with a Trypanosoma cruzi-like strain isolated from a bat: predictive factors for involvement of eosinophiles in tissue damage.

机构信息

Parasitology Division, Department of Biological Sciences, Universidade Federal do Triângulo Mineiro, Uberaba, Brazil.

出版信息

Vector Borne Zoonotic Dis. 2010 Dec;10(10):989-97. doi: 10.1089/vbz.2009.0185. Epub 2010 May 10.

DOI:10.1089/vbz.2009.0185
PMID:20455782
Abstract

The granules of eosinophiles are cytotoxic to Trypanosoma cruzi trypomastigote and amastigote forms and to several cell types of the host, revealing their role in either parasite elimination or the production of tissue lesions. In this study, we evaluated the biological characteristics of T. cruzi infection that are responsible for the increase in tissue eosinophile levels in mice previously immunized with a bat isolated T. cruzi-like strain that does not infect mice. Nonisogeneic mice were divided into 24 groups that received from zero to three inoculations of T. cruzi-like RM1 strain, with or without adjuvant, followed by challenge with T. cruzi VIC or JG strains. Uni- and multivariate comparisons were performed comparing the tissue eosinophile levels with the parasitemia peak, severity of myositis in skeletal muscle, phase of infection, and the immunization strategies induced by the T. cruzi-like strain (adjuvant, number of reinoculations, and parasites). Although the severity of inflammation was higher in the acute phase, the score of tissue eosinophiles was similar in the acute and chronic phases of infection. In addition, there was a positive correlation among eosinophile levels and parasitemia peak. In the chronic phase, a greater eosinophile count was accompanied by an augmentation of myositis. Regardless of the phase of infection, we observed a positive correlation between the intensity of eosinophile infiltration and the number of sensitizations with T. cruzi-like strain. The multivariate analysis showed that the peak of parasitemia, number of inoculations with the T. cruzi-like strain, and severity of myositis were associated with greater tissue eosinophilia, in comparison with adjuvant, T. cruzi strains used in the challenge or tissue parasitism. Therefore, tissue eosinophile levels proved to be an important parameter in the pathogenesis of experimental Chagas disease in the acute and chronic phases of infection and might be related to reinfections, parasite multiplication ability, and severity of inflammatory process.

摘要

嗜酸性粒细胞的颗粒对克氏锥虫的锥虫和变形体形式以及宿主的几种细胞类型具有细胞毒性,这表明它们在寄生虫消除或组织损伤的产生中发挥作用。在这项研究中,我们评估了导致先前用一种不感染小鼠的蝙蝠分离的克氏锥虫样株免疫的小鼠组织嗜酸性粒细胞水平增加的克氏锥虫感染的生物学特征。非同源小鼠分为 24 组,每组接受 0 到 3 次克氏锥虫样 RM1 株的接种,有或没有佐剂,然后用克氏锥虫 VIC 或 JG 株进行挑战。通过比较组织嗜酸性粒细胞水平与寄生虫血症峰值、骨骼肌肌炎严重程度、感染阶段以及克氏锥虫样株诱导的免疫策略(佐剂、再接种次数和寄生虫)进行了单变量和多变量比较。尽管在急性期炎症更严重,但在感染的急性期和慢性期,组织嗜酸性粒细胞的评分相似。此外,嗜酸性粒细胞水平与寄生虫血症峰值之间存在正相关。在慢性期,更多的嗜酸性粒细胞计数伴随着肌炎的加剧。无论感染阶段如何,我们都观察到嗜酸性粒细胞浸润的强度与克氏锥虫样株的致敏次数之间存在正相关。多变量分析表明,与佐剂、用于挑战的克氏锥虫株或组织寄生虫相比,寄生虫血症峰值、克氏锥虫样株接种次数和肌炎严重程度与组织嗜酸性粒细胞增多相关。因此,组织嗜酸性粒细胞水平被证明是感染的急性和慢性阶段实验性恰加斯病发病机制的一个重要参数,并且可能与再感染、寄生虫增殖能力和炎症过程的严重程度有关。

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