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首页> 外文期刊>Immunology: An Official Journal of the British Society for Immunology >Mast cell-macrophage dynamics in modulation of dengue virus infection in skin
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Mast cell-macrophage dynamics in modulation of dengue virus infection in skin

机译：肥大细胞巨噬细胞动力学调节皮肤登革热病毒感染

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Dengue virus (DENV) infection causes dengue fever, dengue haemorrhagic fever, or dengue shock syndrome. Mast cells have been speculated to play a role in DENV disease although their precise roles are unclear. In this study, we used mast cell-deficient Kit(W-sh/W-sh) mice to investigate the involvement of mast cells after intradermal DENV infection. An approximately two- to three-fold higher level of DENV NS3 antigen was detected at the skin inoculation site in DENV-infected Kit(W-sh/W-sh) mice than in DENV-infected wild-type (WT) mice (using a dose of 1x10(9) plaque-forming units/mouse). Moreover, as an indicator of heightened pathogenesis, a more prolonged bleeding time was observed in DENV-infected Kit(W-sh/W-sh) mice than in WT mice. Monocytes/macrophages are considered to be important targets for DENV infection, so we investigated the susceptibility and chemokine response of DENV-infected peritoneal macrophages from Kit(W-sh/W-sh) and WT mice both exvivo and invivo. There was a tendency for higher DENV infection and higher secretion of CCL2 (MCP-1) from peritoneal macrophages isolated from Kit(W-sh/W-sh) mice than those from WT mice. In vivo studies using intradermal inoculation of DENV showed about twofold higher levels of infiltrating macrophages and CCL2 (MCP-1) at the inoculation site in both mock control and DENV-inoculated Kit(W-sh/W-sh) mice than in corresponding WT mice. In summary, compared with WT mice, Kit(W-sh/W-sh) mice show enhanced DENV infection and macrophage infiltration at the skin inoculation site as well as increased DENV-associated bleeding time. The results indicate an intriguing interplay between mast cells and tissue macrophages to restrict DENV replication in the skin.
机译：登革热病毒（DENV）感染会导致登革热，登革出血热或登革热休克综合征。尽管肥大细胞的确切作用尚不清楚，但据推测肥大细胞在DENV疾病中起作用。在这项研究中，我们使用肥大细胞缺陷试剂盒（W-sh / W-sh）小鼠来研究皮内DENV感染后肥大细胞的参与。在DENV感染的Kit（W-sh / W-sh）小鼠的皮肤接种部位检测到的DENV NS3抗原水平大约是DENV感染的野生型（WT）小鼠的2-3倍1x10（9）斑块形成单位/小鼠的剂量）。此外，作为增加发病机理的指标，与野生型小鼠相比，在DENV感染的Kit（W-sh / W-sh）小鼠中观察到更长的出血时间。单核细胞/巨噬细胞被认为是DENV感染的重要靶标，因此我们研究了Kit（W-sh / W-sh）和WT小鼠体内和体外感染DENV感染的腹膜巨噬细胞的敏感性和趋化因子反应。与从WT小鼠相比，从Kit（W-sh / W-sh）小鼠分离的腹膜巨噬细胞中存在更高的DENV感染和更高的CCL2（MCP-1）分泌的趋势。使用DENV皮内接种的体内研究显示，模拟对照组和DENV接种的Kit（W-sh / W-sh）小鼠的接种部位的浸润巨噬细胞和CCL2（MCP-1）的水平比相应的WT高约两倍老鼠。总之，与野生型小鼠相比，Kit（W-sh / W-sh）小鼠在皮肤接种部位表现出增强的DENV感染和巨噬细胞浸润，以及与DENV相关的出血时间增加。结果表明肥大细胞和组织巨噬细胞之间的有趣相互作用限制了DENV在皮肤中的复制。

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