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埃塞俄比亚皮肤利什曼病患者暴露于埃塞俄比亚利什曼原虫后促炎细胞因子和趋化因子的产生增加。

Enhanced production of pro-inflammatory cytokines and chemokines in Ethiopian cutaneous leishmaniasis upon exposure to Leishmania aethiopica.

作者信息

Chanyalew Menberework, Abebe Markos, Endale Birtukan, Girma Selfu, Tasew Geremew, van Zandbergen Ger, Ritter Uwe, Gadisa Endalamaw, Aseffa Abraham, Laskay Tamás

机构信息

Research and Innovation Division, Armauer Hansen Research Institute, P.O. Box 1005, Addis Ababa, Ethiopia.

Research and Innovation Division, Armauer Hansen Research Institute, P.O. Box 1005, Addis Ababa, Ethiopia.

出版信息

Cytokine. 2021 Sep;145:155289. doi: 10.1016/j.cyto.2020.155289. Epub 2020 Sep 18.

Abstract

The clinical course and outcome of cutaneous leishmaniasis (CL) vary due to the infecting Leishmania species and host genetic makeup that result in different immune responses against the parasites. The host immune response to Leishmania aethiopica (L.aethiopica), the causative agent of CL in Ethiopia, is poorly understood. To contribute to the understanding of the protective immune response in CL due to L.aethiopica, we characterized the cytokine response to L. aethiopica in patients with the localized form of CL (LCL) and age-and sex-matched apparently healthy controls. By applying a whole blood based in vitro culture we found enhanced release of TNF, IL-6, MCP-1 or CCL2, IP-10 or CXCL10, MIP-1β or CCL4 and IL-8 or CXCL8- but not of IL-10CL patients in response to L. aethiopica compared to the controls. No difference was observed between LCL cases and controls in the secretion of these cytokines and chemokines in whole blood cultures treated with the TLR-ligands LPS, MALP-2 or polyI: C. The observed increased secretion of the pro-inflammatory cytokines/chemokines reflects an enhanced response against the parasites by LCL patients as compared to healthy controls rather than a generally enhanced ability of blood leukocytes from LCL patients to respond to microbial constituents. Our findings suggest that the enhanced production of pro-inflammatory cytokines/chemokines is associated with localized cutaneous leishmaniasis caused by L.aethiopica.

摘要

皮肤利什曼病(CL)的临床病程和结局因感染的利什曼原虫种类以及宿主基因构成的不同而有所差异,这些因素会导致针对寄生虫的免疫反应各不相同。人们对宿主针对埃塞俄比亚利什曼原虫(L.aethiopica,埃塞俄比亚CL的病原体)的免疫反应了解甚少。为了有助于理解由埃塞俄比亚利什曼原虫引起的CL中的保护性免疫反应,我们对局限性皮肤利什曼病(LCL)患者以及年龄和性别匹配的明显健康对照者针对埃塞俄比亚利什曼原虫的细胞因子反应进行了特征分析。通过应用基于全血的体外培养,我们发现与对照组相比,LCL患者在接触埃塞俄比亚利什曼原虫后,TNF、IL-6、MCP-1或CCL2、IP-10或CXCL10、MIP-1β或CCL4以及IL-8或CXCL8的释放增加,但IL-10没有增加。在用TLR配体LPS、MALP-2或聚肌苷酸:胞苷酸处理的全血培养物中,LCL病例与对照在这些细胞因子和趋化因子的分泌方面未观察到差异。观察到的促炎细胞因子/趋化因子分泌增加反映出与健康对照相比,LCL患者针对寄生虫的反应增强,而不是LCL患者血液白细胞对微生物成分作出反应的能力普遍增强。我们的研究结果表明,促炎细胞因子/趋化因子的产生增加与埃塞俄比亚利什曼原虫引起的局限性皮肤利什曼病相关。

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