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针对白喉毒素介导的耗竭的免疫反应使 CD11c-DTR(tg) 模型在研究细菌性胃肠道感染中的应用变得复杂。

Immune response to diphtheria toxin-mediated depletion complicates the use of the CD11c-DTR(tg) model for studies of bacterial gastrointestinal infections.

机构信息

Department of Molecular Biology, Umeå Centre for Microbial Research, Laboratory for Molecular Infection Medicine Sweden, Umeå University, 901 87 Umeå, Sweden.

出版信息

Microb Pathog. 2012 Sep;53(3-4):154-61. doi: 10.1016/j.micpath.2012.06.004. Epub 2012 Jul 6.

DOI:10.1016/j.micpath.2012.06.004
PMID:22771374
Abstract

Dendritic cells play an important role in the immune response against pathogens, as they are responsible for the activation and control of both innate and adaptive immune responses. The CD11c-DTR(tg) model, which allows transient elimination of dendritic cells by diphtheria toxin-treatment (DTx), has been extensively used to study the importance of this immune cell during steady-state and infection conditions in mice. Infecting dendritic cell-depleted mice orally with Yersinia pseudotuberculosis results in a markedly reduced level of infection compared with infection of non-depleted mice. We show here that it is not the lack of dendritic cells per se that is responsible for the reduced infection efficiency, instead it is an immune response induced by the DTx-treatment that prevents the bacteria from establishing colonization in Peyer's patches. The DTx-induced depletion initiates an immune response, with elevated serum levels of keratinocyte-derived cytokine (KC) and recruitment of polymorphonuclear neutrophils to dendritic cell-containing organs, such as Peyer's patches. Since the window for having an animal depleted of dendritic cells is limited in time for this model, the DTx-mediated effect on the immune system complicates the use of this model in studies of early events during bacterial infections.

摘要

树突状细胞在针对病原体的免疫反应中发挥着重要作用,因为它们负责激活和控制先天免疫和适应性免疫反应。CD11c-DTR(tg)模型允许通过白喉毒素处理(DTx)瞬时消除树突状细胞,已被广泛用于研究在小鼠的稳态和感染条件下这种免疫细胞的重要性。与未耗尽树突状细胞的小鼠相比,用假结核耶尔森氏菌经口感染耗尽树突状细胞的小鼠会导致感染水平明显降低。我们在这里表明,导致感染效率降低的不是树突状细胞本身的缺乏,而是 DTx 处理诱导的免疫反应阻止了细菌在派尔氏斑中定植。DTx 诱导的消耗引发了免疫反应,角质细胞衍生细胞因子(KC)的血清水平升高,多形核中性粒细胞募集到含有树突状细胞的器官,如派尔氏斑。由于该模型中用于耗尽树突状细胞的动物的时间窗口有限,DTx 对免疫系统的影响使该模型在研究细菌感染早期事件时的应用变得复杂。

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