Fascin confers resistance to Listeria infection in dendritic cells.
Fascin confers resistance to Listeria infection in dendritic cells.
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DOI：
10.4049/jimmunol.1300498
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发表时间：
2013-12-15
期刊：
影响因子：
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通讯作者：
Yamashiro S
中科院分区：
文献类型：
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作者：
Matsumura F;Yamakita Y;Starovoytov V;Yamashiro S
抗原提呈树突状细胞(DC)必须在细菌感染后存活，才能将抗原信息呈递给初始T细胞。DC对单核细胞增多性李斯特菌的抵抗力强于巨噬细胞，这说明DC具有更强的宿主防御能力。然而，这种抗性的分子机制尚不清楚。我们发现，与令人着迷的1基因敲除DC相比，李斯特菌在野生型DC中的复制速度更慢。这一发现意义重大，因为在树突状细胞成熟时，一种肌动蛋白捆绑蛋白SENSE1被特异性地大量诱导，而不是包括巨噬细胞和中性粒细胞在内的其他血细胞。李斯特菌感染使野生型DC的吞噬小体比Socor1基因敲除的DCs更酸性，这表明Fezen1促进了吞噬融合以杀灭吞噬细胞中的李斯特菌。我们进一步发现，无论是在体内还是在体外，Socor1都与自噬体标记物LC3结合。在野生型DC中，与Lc3相关的李斯特菌在更大程度上与Socent1KO DCs有关，这表明Socor1促进了自噬以根除细胞质李斯特菌。综上所述，我们的结果表明，在李斯特菌感染期间，Socor1在DC的生存中发挥着关键作用，使DC能够发挥先天免疫和获得性免疫功能。
Antigen-presenting dendritic cells (DCs) must survive bacterial infection in order to present antigen information to naive T-cells. The greater ability of DC's host defense is evident from the report that DCs are more resistant to Listeria monocytogenes than macrophages. However, the molecular mechanism of this resistance is unclear. We found that Listeria replicate more slowly in wild type DCs compared to fascin1 knockout DCs. This finding is significant because fascin1, an actin bundling protein, is specifically and greatly induced upon maturation of dendritic cells, but not other blood cells including macrophages and neutrophils. Infection by Listeria makes phagosomes more acidic in wild type DCs than in fascin1 knockout DCs, suggesting that fascin1 facilitates phagolysosomal fusion for killing of phagocytosed Listeria. We further found that fascin1 binds to LC3, an autophagosome marker, both in vivo and in vitro. Listeria are associated with LC3 to a greater extent in wild type DCs than in fascin1 KO DCs, suggesting that fascin1 facilitates autophagy for eradication of cytoplasmic Listeria. Taken together, our results suggest that fascin1 plays critical roles in the survival of DCs during Listeria infection, allowing DCs to function in innate and adaptive immunity.