Histopathological and immunohistochemical characterisation of hepatic granulomas in Leishmania donovani-infected BALB/c mice: a time-course study.
Histopathological and immunohistochemical characterisation of hepatic granulomas in Leishmania donovani-infected BALB/c mice: a time-course study.
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DOI：
10.1186/s13071-018-2624-z
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发表时间：
2018-01-31
影响因子：
3.2
通讯作者：
Seifert K
中科院分区：
文献类型：
--
作者：
Salguero FJ;Garcia-Jimenez WL;Lima I;Seifert K
内脏利什曼病 (VL) 是一种被忽视的热带病 (NTD)，由细胞内原生动物寄生虫杜氏利什曼原虫和婴儿利什曼原虫引起。如果不及时治疗，有症状的 VL 被认为是致命的。目前，还没有有效的疫苗被许可用于人类，并且可用的化疗方法也有局限性。了解控制感染所需的局部免疫机制是开发有效疫苗和治疗方法的关键因素。我们研究了实验性 VL 中肝脏中典型肉芽肿性病变随时间的发展情况以及局部免疫反应。 BALB/c 小鼠用 2 × 107 杜氏乳杆菌无鞭毛体 (MHOM/ET/67/HU3) 进行静脉内感染，并在感染后 15、35 和 63 天 (dpi) 处死。采用组织病理学和免疫组织化学技术检测利什曼原虫抗原、选定的细胞类型，包括 B 和 T 淋巴细胞、巨噬细胞和中性粒细胞（CD45R-B220+、CD3+、F4/80+ 和 Ly-6G+）以及 iNOS。早在感染后 15 dpi 就在所有受感染动物的肝脏中发现了肉芽肿性病变。使用三个类别对肝肉芽肿进行分类（未成熟、成熟和透明）。仅从 35 dpi 起检测到透明肉芽肿。无论 dpi 如何，库普弗细胞 (F4/80+) 在未成熟肉芽肿中占主导地位。尽管如此，最高表达速度为 63 dpi。 iNOS 阳性染色主要在融合 Kupffer 细胞的细胞质中观察到，在 35 dpi 时观察到最高表达。 T细胞（CD3+）和B细胞（CD45R-B220+）在更晚期的肉芽肿阶段占主导地位，可能与获得性免疫的建立有关。中性粒细胞 (Ly-6G+) 主要在成熟肉芽肿中观察到，在 15 dpi 时表达最高。与其他细胞类型相比，中性粒细胞的数量较低，尤其是在较晚的时间点。我们的结果反映了巨噬细胞在感染早期阶段的作用以及淋巴细胞反应的建立以控制更晚期的感染。
Visceral leishmaniasis (VL) is a neglected tropical disease (NTD), caused by the intracellular protozoan parasites Leishmania donovani and Leishmania infantum. Symptomatic VL is considered fatal when left untreated. At present, there is no effective vaccine licensed for human use and available chemotherapies have limitations. Understanding the local immune mechanisms required for the control of infection is a key factor for developing effective vaccines and therapeutics. We have investigated the development of the typical granulomatous lesions in the liver in experimental VL over time, together with the local immune responses. BALB/c mice were infected intravenously with a dose of 2 × 107 L. donovani amastigotes (MHOM/ET/67/HU3) and sacrificed at 15, 35 and 63 days post-infection (dpi). Histopathology and immunohistochemical techniques were used for the detection of Leishmania antigen, selected cell types including B and T lymphocytes, macrophages and neutrophils (CD45R-B220+, CD3+, F4/80+ and Ly-6G+) and iNOS. Granulomatous lesions were identified as early as 15 dpi in the livers of all infected animals. Three categories were used to classify liver granulomas (immature, mature and clear). Clear granulomas were exclusively detected from 35 dpi onwards. Kupffer cells (F4/80+) were predominant in immature granulomas, regardless of the dpi. Nonetheless, the highest expression was found 63 dpi. Positive staining for iNOS was mainly observed in the cytoplasm of fused Kupffer cells and the highest expression observed at 35 dpi. T cells (CD3+) and B cells (CD45R-B220+) were predominant in more advanced granuloma stages, probably related to the establishment of acquired immunity. Neutrophils (Ly-6G+) were predominantly observed in mature granulomas with the highest expression at 15 dpi. Neutrophils were lower in numbers compared to other cell types, particularly at later time points. Our results reflect the role of macrophages during the early stage of infection and the establishment of a lymphocytic response to control the infection in more advanced stages.
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影响因子：
3.1
作者：
CROCKER, PR;BLACKWELL, JM;BRADLEY, DJ
通讯作者：
BRADLEY, DJ
影响因子：
2.2
作者：
Carrión, J;Nieto, A;Alonso, C
通讯作者：
Alonso, C
影响因子：
7.7
作者：
Pigott DM;Golding N;Mylne A;Huang Z;Henry AJ;Weiss DJ;Brady OJ;Kraemer MU;Smith DL;Moyes CL;Bhatt S;Gething PW;Horby PW;Bogoch II;Brownstein JS;Mekaru SR;Tatem AJ;Khan K;Hay SI
通讯作者：
Hay SI
影响因子：
3.1
作者：
McFarlane, Emma;Perez, Cynthia;Tacchini-Cottier, Fabienne
通讯作者：
Tacchini-Cottier, Fabienne
影响因子：
1.6
作者：
Hicks, D. J.;Johnson, L.;Wangoo, A.
通讯作者：
Wangoo, A.