Dendritic Cell-Derived IL-12p40 Homodimer Contributes to Susceptibility in Cutaneous Leishmaniasis in BALB/c Mice1
Dendritic Cell-Derived IL-12p40 Homodimer Contributes to Susceptibility in Cutaneous Leishmaniasis in BALB/c Mice1
复制标题
树突状细胞衍生的 IL-12p40 同二聚体导致 BALB/c 小鼠皮肤利什曼病的易感性1
作者：
A. Nigg;S. Zahn;Dominik Rückerl;C. Hölscher;T. Yoshimoto;J. Ehrchen;F. Wölbing;M. Udey;E. von Stebut
抗利什曼原虫C57 BL/6小鼠的保护作用是由Th 1细胞介导的，而BALB/c小鼠的易感性是Th 2细胞发育的结果。IL-12的释放。主要感染的树突状细胞（DC）关键地参与Th 1细胞的分化。以前，我们报道了DC衍生因子产生的菌株差异，例如，IL-1αβ是导致不同疾病结局的部分原因。在本研究中，我们更详细地分析了DC中IL-12的释放。来自C57 BL/6和BALB/c小鼠的刺激DC释放相当量的IL-12 p40和p70。在IL-4缺乏的情况下，BALB/c DC产生的IL-12 p40显著高于C57 BL/6 DC。通过Western印迹和ELISA的详细分析显示，在DC上清液中检测到的IL-12 p40的十分之一作为IL-12拮抗剂IL-12 p40同型二聚体（IL-12 p80）释放。BALB/c DC在体外和体内释放的IL-12 p80是C57 BL/6 DC的102倍。在感染后的前3天内局部注射IL-12 p80导致两个L.主要感染BALB/c或C57 BL/6小鼠，在较高的病变寄生虫负荷，并减少Th 1细胞因子的产生。最后，以p40过表达为特征的IL-12 p40转基因C57 BL/6小鼠显示血清IL-12 p80水平升高和疾病易感性增强。因此，除了IL-1αβ之外，其他DC衍生因子（例如IL-12 p80）释放的菌株依赖性差异可能会影响遗传决定的疾病结局。
Protection against Leishmania major in resistant C57BL/6 mice is mediated by Th1 cells, whereas susceptibility in BALB/c mice is the result of Th2 development. IL-12 release by L. major-infected dendritic cells (DC) is critically involved in differentiation of Th1 cells. Previously, we reported that strain differences in the production of DC-derived factors, e.g., IL-1αβ, are in part responsible for disparate disease outcome. In the present study, we analyzed the release of IL-12 from DC in more detail. Stimulated DC from C57BL/6 and BALB/c mice released comparable amounts of IL-12p40 and p70. In the absence of IL-4, BALB/c DC produced significantly more IL-12p40 than C57BL/6 DC. Detailed analyses by Western blot and ELISA revealed that one-tenth of IL-12p40 detected in DC supernatants was released as the IL-12 antagonist IL-12p40 homodimer (IL-12p80). BALB/c DC released ∼2-fold more IL-12p80 than C57BL/6 DC both in vitro and in vivo. Local injection of IL-12p80 during the first 3 days after infection resulted in increased lesion volumes for several weeks in both L. major-infected BALB/c or C57BL/6 mice, in higher lesional parasite burdens, and decreased Th1-cytokine production. Finally, IL-12p40-transgenic C57BL/6 mice characterized by overexpression of p40 showed increased levels of serum IL-12p80 and enhanced disease susceptibility. Thus, in addition to IL-1αβ, strain-dependent differences in the release of other DC-derived factors such as IL-12p80 may influence genetically determined disease outcome.
影响因子：
4.4
作者：
J. Piccotti;S. Chan;Kewang Li;E. Eichwald;D. Bishop
通讯作者：
J. Piccotti;S. Chan;Kewang Li;E. Eichwald;D. Bishop
针对重大利什曼原虫感染的 Th1 依赖性免疫力的要求。
DOI：
10.1016/j.micinf.2004.05.024
发表时间：
2004
期刊：
Microbes and infection / Institut Pasteur
影响因子：
--
作者：
vonStebut,Esther;Udey,MarkC
通讯作者：
Udey,MarkC
IL-12 p40 同二聚体的体内产生和功能。
DOI：
--
发表时间：
1997
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Heinzel,FP;Hujer,AM;Ahmed,FN;Rerko,RM
通讯作者：
Rerko,RM