Impact of Toxoplasma gondii on Dendritic Cell Subset Function in the Intestinal Mucosa.

Impact of Toxoplasma gondii on Dendritic Cell Subset Function in the Intestinal Mucosa.
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DOI:
10.4049/jimmunol.1501137
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发表时间:
2015-09-15
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
通讯作者:
Denkers EY
Denkers EY
中科院分区:
其他
文献类型:
--
作者:
Cohen SB;Denkers EY

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粘膜DC亚群在免疫和炎症中的作用尚不清楚。在这里,我们根据CD103和CD11b的表达定义了存在于固有层和肠系膜淋巴结室内的四个DC亚群。利用IL-12p40YFP(Yet40)报告小鼠,我们发现CD103+CD11b−粘膜DC是体内产生IL-12p40的主要来源,但我们也发现CD103−CD11b−粘膜DC是产生这种细胞因子的新群体。CD103阴性的DC以CD11b+DC感染为主。含有寄生虫的固有层DC对IL-12p40呈阴性反应,相反,细胞因子的产生严格来说是未感染细胞的特性。我们还发现,以ALDH活性衡量,维生素A代谢在CD103+CD11b+DC中优先被发现,并在感染期间在所有粘膜DC亚群中强烈下调。最后,在感染过程中,固有层DC亚群的总凋亡率增加。总而言之,这些结果强调了肠道弓形虫感染在整个种群水平和个体亚群水平上改变粘膜DC活性的能力。
The function of mucosal DC subsets in immunity and inflammation is not well understood. Here we define four DC subsets present within the lamina propria and mesenteric lymph node compartments based upon expression of CD103 and CD11b. Using IL-12p40 YFP (Yet40) reporter mice, we show that CD103+CD11b− mucosal DC are primary in vivo sources of IL-12p40 but we also identified CD103−CD11b− mucosal DC as a novel population producing this cytokine. Infection was preferentially found in CD11b+ DC negative for CD103. Lamina propria DC containing parasites were negative for IL-12p40 and instead production of the cytokine was strictly a property of noninfected cells. We also show that vitamin A metabolism, as measured by ALDH activity, was preferentially found in CD103+CD11b+ DC, and was strongly downregulated in all mucosal DC subsets during infection. Finally, overall apoptosis of lamina propria DC subsets was increased during infection. Combined, these results highlight the ability of intestinal Toxoplasma infection to alter mucosal DC activity at both the whole population level and at the level of individual subsets.