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IL-10-Dependent Crosstalk between Murine Marginal Zone B Cells, Macrophages, and CD8α+ Dendritic Cells Promotes Listeria monocytogenes Infection.
Immunity ( IF 25.5 ) Pub Date : 2019-06-20 , DOI: 10.1016/j.immuni.2019.05.011
Dong Liu 1 , Xiangyun Yin 1 , Sam J Olyha 1 , Manuela Sales L Nascimento 2 , Pei Chen 3 , Theresa White 4 , Uthaman Gowthaman 1 , Tingting Zhang 5 , Jake A Gertie 1 , Biyan Zhang 1 , Lan Xu 1 , Marina Yurieva 6 , Lesley Devine 7 , Adam Williams 8 , Stephanie C Eisenbarth 1
Affiliation  

Type 1 CD8α+ conventional dendritic cells (cDC1s) are required for CD8+ T cell priming but, paradoxically, promote splenic Listeria monocytogenes infection. Using mice with impaired cDC2 function, we ruled out a role for cDC2s in this process and instead discovered an interleukin-10 (IL-10)-dependent cellular crosstalk in the marginal zone (MZ) that promoted bacterial infection. Mice lacking the guanine nucleotide exchange factor DOCK8 or CD19 lost IL-10-producing MZ B cells and were resistant to Listeria. IL-10 increased intracellular Listeria in cDC1s indirectly by reducing inducible nitric oxide synthase expression early after infection and increasing intracellular Listeria in MZ metallophilic macrophages (MMMs). These MMMs trans-infected cDC1s, which, in turn, transported Listeria into the white pulp to prime CD8+ T cells. However, this also facilitated bacterial expansion. Therefore, IL-10-mediated crosstalk between B cells, macrophages, and cDC1s in the MZ promotes both Listeria infection and CD8+ T cell activation.

中文翻译:

小鼠边缘区B细胞,巨噬细胞和CD8α+树突状细胞之间的IL-10依赖性串扰会促进单核细胞增多性李斯特菌感染。

CD8 + T细胞启动需要1型CD8α+常规树突状细胞(cDC1s),但自相矛盾的是,它会促进脾单核细胞增生性李斯特菌感染。使用具有受损cDC2功能的小鼠,我们排除了cDC2s在此过程中的作用,而是在边缘区域(MZ)中发现了白介素10(IL-10)依赖性细胞串扰,从而促进细菌感染。缺少鸟嘌呤核苷酸交换因子DOCK8或CD19的小鼠失去产生IL-10的MZ B细胞,并对李斯特菌具有抗性。IL-10通过在感染后早期降低诱导型一氧化氮合酶的表达并增加MZ嗜金属巨噬细胞(MMM)中的细胞内李斯特菌间接增加cDC1s中的细胞内李斯特菌。这些MMM会感染cDC1,然后将利斯特氏菌转运到白色果肉中以引发CD8 + T细胞。然而,这也促进了细菌的繁殖。因此,MZ中B细胞,巨噬细胞和cDC1s之间的IL-10介导的串扰既促进李斯特菌感染也促进CD8 + T细胞活化。
更新日期:2019-06-20
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