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C3H/HeNJ对波摩那群问号钩端螺旋体的亚致死感染。

Sublethal infection of C3H/HeNJ against Leptospira interrogans serovar Pomona.

作者信息

Krangvichian Pratomporn, Nakornpakdee Yaowarin, Sangjun Noppadon, Komanee Pat, Techawiwattanaboon Teerasit, Patarakul Kanitha

机构信息

Medical Microbiology, Interdisciplinary Program, Graduate School, Chulalongkorn University, Pathumwan, Bangkok, 10330 Thailand; Chula Vaccine Research Center (Chula VRC), Center of Excellence in Vaccine Research and Development, Chulalongkorn University, Pathumwan, Bangkok, 10330 Thailand.

Department of Pathobiology, Faculty of Science, Mahidol University, Ratchathewi, Bangkok, 10400 Thailand.

出版信息

Acta Trop. 2023 Feb;238:106701. doi: 10.1016/j.actatropica.2022.106701. Epub 2022 Oct 8.

Abstract

Leptospirosis is a worldwide zoonotic disease caused by pathogenic Leptospira spp. Leptospires can infect a variety of mammalian species. Golden Syrian hamsters are mostly used to study acute leptospirosis. However, the immunopathogenic mechanism is poorly understood because immunological reagents for hamsters are limited. This study aimed to establish C3H/HeNJ mice as an animal model for leptospirosis. Five-week-old C3H/HeNJ mice were infected with either low (10 cells) or high (10 cells) inoculum dose of Leptospira interrogans serovar Pomona. All mice were investigated for survival rate, leptospiral load and histopathology of target organs, antibody levels, and cytokine production (IFN-γ, IL-6 and IL-10) at day 28 post-infection. All infected mice survived and did not develop acute lethal infection. However, C3H/HeNJ mice infected with 10 cells of leptospires showed kidney colonization of leptospires and pathological changes in the lung and kidney including renal fibrosis. The glomerular size in PAS-D stained kidney tissues of C3H/HeNJ mice infected with 10 cells of leptospires was significantly reduced compared to that of mice infected with 10 cells of leptospires and non-infected mice. High-dose leptospires induced significantly greater levels of IFN-gamma and IL-6 than low-dose leptospires, but IL-10 level was not significantly different. Moreover, 10 leptospiral cells induced predominant IgG2a isotype suggesting Th1-like response. These results suggest that C3H/HeNJ mice may be used as a sublethal model of leptospirosis.

摘要

钩端螺旋体病是一种由致病性钩端螺旋体属引起的全球性人畜共患病。钩端螺旋体能感染多种哺乳动物。金黄叙利亚仓鼠大多用于研究急性钩端螺旋体病。然而,由于用于仓鼠的免疫试剂有限,其免疫致病机制尚不清楚。本研究旨在将C3H/HeNJ小鼠建立为钩端螺旋体病的动物模型。对5周龄的C3H/HeNJ小鼠接种低剂量(10个菌细胞)或高剂量(10个菌细胞)的波摩那型问号钩端螺旋体。在感染后第28天,对所有小鼠进行存活率、钩端螺旋体载量、靶器官组织病理学、抗体水平和细胞因子产生(IFN-γ、IL-6和IL-10)的检测。所有感染小鼠均存活,未发生急性致死性感染。然而,感染10个菌细胞钩端螺旋体的C3H/HeNJ小鼠出现钩端螺旋体在肾脏定植,以及肺和肾脏的病理变化,包括肾纤维化。与感染10个菌细胞钩端螺旋体的小鼠和未感染小鼠相比,感染10个菌细胞钩端螺旋体的C3H/HeNJ小鼠经PAS-D染色的肾脏组织中肾小球大小显著减小。高剂量钩端螺旋体诱导产生的IFN-γ和IL-6水平明显高于低剂量钩端螺旋体,但IL-10水平无显著差异。此外,10个钩端螺旋体细胞诱导产生以IgG2a为主的同种型,提示类似Th1的反应。这些结果表明,C3H/HeNJ小鼠可作为钩端螺旋体病的亚致死模型。

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