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对重症联合免疫缺陷小鼠感染杜氏利什曼原虫期间细胞因子产生的体内分析。

An in vivo analysis of cytokine production during Leishmania donovani infection in scid mice.

作者信息

Engwerda C R, Smelt S C, Kaye P M

机构信息

Department of Medical Parasitology, London School of Hygiene and Tropical Medicine, UK.

出版信息

Exp Parasitol. 1996 Nov;84(2):195-202. doi: 10.1006/expr.1996.0105.

Abstract

Leishmania donovani, the causative agent of visceral leishmaniasis, fails to induce NK cell activation in scid mice. In order to further our understanding of the host response to L. donovani, we analysed cytokine mRNA accumulation and TNF alpha protein synthesis in the liver of scid and BALB/c mice infected with this parasite. scid mice infected with L. donovani exhibited very little proinflammatory response, as measured by cytokine mRNA accumulation and TNF alpha protein expression, supporting the notion of a relatively "quiet" interaction between L. donovani and macrophages in these animals. In contrast, immunocompetent BALB/c mice were found to generate an early IFN gamma response, coincident with a rise in IL-2 mRNA levels and elaboration of a tissue response involving TNF alpha production by infected Kupffer cells. These results extend our understanding of the response of BALB/c and scid mice to L. donovani infection and highlight the value of cytokine analysis at both the tissue and cellular levels.

摘要

杜氏利什曼原虫是内脏利什曼病的病原体,在严重联合免疫缺陷(scid)小鼠中无法诱导自然杀伤细胞激活。为了进一步了解宿主对杜氏利什曼原虫的反应,我们分析了感染该寄生虫的scid小鼠和BALB/c小鼠肝脏中细胞因子mRNA积累和肿瘤坏死因子α(TNFα)蛋白合成情况。通过细胞因子mRNA积累和TNFα蛋白表达测定,感染杜氏利什曼原虫的scid小鼠表现出极少的促炎反应,这支持了在这些动物中杜氏利什曼原虫与巨噬细胞之间存在相对“安静”相互作用的观点。相比之下,发现具有免疫能力的BALB/c小鼠会产生早期干扰素γ反应,这与白细胞介素-2 mRNA水平升高以及受感染枯否细胞产生TNFα所引发的组织反应同时出现。这些结果扩展了我们对BALB/c和scid小鼠对杜氏利什曼原虫感染反应的理解,并突出了在组织和细胞水平进行细胞因子分析的价值。

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