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实验感染小鼠体内组织特异性犬弓首蛔虫幼虫移行与宿主免疫应答

Organ-specific Toxocara canis larvae migration and host immune response in experimentally infected mice.

机构信息

Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam 13620, Korea.

Department of Microbiology, Dongguk University College of Medicine, Gyeongju 38066, Korea.

出版信息

Parasites Hosts Dis. 2024 May;62(2):243-250. doi: 10.3347/PHD.23125. Epub 2024 May 27.

Abstract

We investigated organ specific Toxocara canis larval migration in mice infected with T. canis larvae. We observed the worm burden and systemic immune responses. Three groups of BALB/c mice (n=5 each) were orally administered 1,000 T. canis 2nd stage larvae to induce larva migrans. Mice were sacrificed at 1, 3, and 5 weeks post-infection. Liver, lung, brain, and eye tissues were collected. Tissue from 2 mice per group was digested for larval count, while the remaining 3 mice underwent histological analysis. Blood hematology and serology were evaluated and compared to that in a control uninfected group (n=5) to assess the immune response. Cytokine levels in bronchoalveolar lavage (BAL) fluid were also analyzed. We found that, 1 week post-infection, the mean parasite load in the liver (72±7.1), brain (31±4.2), lungs (20±5.7), and eyes (2±0) peaked and stayed constant until the 3 weeks. By 5-week post-infection, the worm burden in the liver and lungs significantly decreased to 10±4.2 and 9±5.7, respectively, while they remained relatively stable in the brain and eyes (18±4.2 and 1±0, respectively). Interestingly, ocular larvae resided in all retinal layers, without notable inflammation in outer retina. Mice infected with T. canis exhibited elevated levels of neutrophils, monocytes, eosinophils, and immunoglobulin E. At 5 weeks post-infection, interleukin (IL)-5 and IL-13 levels were elevated in BAL fluid. Whereas IL-4, IL-10, IL-17, and interferon-γ levels in BAL fluid were similar to that in controls. Our findings demonstrate that a small portion of T. canis larvae migrate to the eyes and brain within the first week of infection. Minimal tissue inflammation was observed, probably due to increase of anti-inflammatory cytokines. This study contributes to our understanding of the histological and immunological responses to T. canis infection in mice, which may have implications to further understand human toxocariasis.

摘要

我们研究了感染犬弓首蛔虫幼虫的小鼠体内特定器官的犬弓首蛔虫幼虫迁移情况。我们观察了虫体负荷和全身免疫反应。将三组 BALB/c 小鼠(每组 5 只)经口给予 1000 条犬弓首蛔虫 2 期幼虫以诱导幼虫移行。感染后 1、3 和 5 周处死小鼠。收集肝、肺、脑和眼组织。每组 2 只小鼠的组织进行幼虫计数,其余 3 只小鼠进行组织学分析。评估和比较血液血液学和血清学与未感染对照(n=5),以评估免疫反应。还分析了支气管肺泡灌洗液(BAL)中的细胞因子水平。我们发现,感染后 1 周,肝(72±7.1)、脑(31±4.2)、肺(20±5.7)和眼(2±0)中的寄生虫负荷达到峰值并保持不变,直到 3 周。感染后 5 周,肝和肺中的虫体负荷分别显著下降至 10±4.2 和 9±5.7,而在脑和眼内则相对稳定(18±4.2 和 1±0)。有趣的是,眼内幼虫存在于所有视网膜层中,外视网膜无明显炎症。感染犬弓首蛔虫的小鼠中性粒细胞、单核细胞、嗜酸性粒细胞和免疫球蛋白 E 水平升高。感染后 5 周,BAL 液中白细胞介素(IL)-5 和 IL-13 水平升高。而 BAL 液中的 IL-4、IL-10、IL-17 和干扰素-γ水平与对照组相似。我们的研究结果表明,在感染后的第一周内,一小部分犬弓首蛔虫幼虫迁移到眼睛和大脑。观察到的组织炎症很少,可能是由于抗炎细胞因子的增加。这项研究有助于我们了解小鼠感染犬弓首蛔虫后的组织学和免疫学反应,这可能对进一步了解人类弓蛔虫病有意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36e4/11150926/98dbe7bbbec2/phd-23125f1.jpg

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