Enhanced antibacterial potential in UBP43-deficient mice against Salmonella typhimurium infection by up-regulation type IIFN signaling
Enhanced antibacterial potential in UBP43-deficient mice against Salmonella typhimurium infection by up-regulation type IIFN signaling
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DOI：
10.4049/jimmunol.175.2.847
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发表时间：
2005-07-15
影响因子：
4.4
通讯作者：
Zhang, DE
中科院分区：
文献类型：
--
作者：
Kim, KI;Malakhova, OA;Zhang, DE
ISG15是一种ifn诱导的泛素样蛋白，其表达和结合靶蛋白在病毒或细菌感染时被显著诱导。我们建立了一个缺乏isg15特异性异肽酶的UBP43敲除小鼠模型来研究蛋白质isg酰化系统的生物学作用。我们报道了UBP43缺陷小鼠对LPS诱导的致死性过敏，并且含有TIR结构域的适配器诱导IFN- β -> IFN调节因子3- > I型IFN是LPS处理后巨噬细胞中诱导蛋白isg酰化和UBP43表达的主要轴。在ubp43（-/-）巨噬细胞中，经过LPS处理，我们检测到ifn刺激基因的表达增加，包括参与先天免疫反应的几种细胞因子和趋化因子的基因。与野生型小鼠相比，ubp43（-/-）小鼠能够更有效地抑制鼠伤寒沙门氏菌的生长。这些结果清楚地证明了ifn信号的两个方面，对病原体有有益的作用，但如果没有严格的控制，就会对身体有害。
ISG15 is an IFN-inducible ubiquitin-like protein andits expression and conjugation to target proteins are dramatically induced upon viral or bacterial infection. We have generated a UBP43 knockout mouse model that is lacking an ISG15-specific isopeptidase to study the biological role of the protein ISGylation system. We report that UBP43-deficient mice are hypersensitive to LPS-induced lethality and that TIR domain-containing adapter inducing IFN-beta -> IFN regulatory factor 3 -> type I IFN is the major axis to induce protein ISGylation and UBP43 expression in macrophages upon LPS treatment. In ubp43(-/-) macrophages, upon LPS treatment we detected increased expression of IFN-stimulated genes, including genes for several cytokines and chemokines involved in the innate immune response. The ubp43(-/-) mice were able to restrict the growth of Salmonella typhimurium more efficiently than wild-type mice. These results clearly demonstrate two aspects of IFN-signaling, a beneficial effect against pathogens but a detriment to the body without strict control.