Cross- presenting dendritic cells are required for control of Leishmania major infection
Cross- presenting dendritic cells are required for control of Leishmania major infection
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DOI：
10.1002/eji.201344242
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发表时间：
2014-05-01
影响因子：
5.4
通讯作者：
Acha-Orbea, Hans
中科院分区：
文献类型：
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作者：
Ashok, Devika;Schuster, Steffen;Acha-Orbea, Hans
利什曼原虫重度感染可在 C57BL/6 小鼠中诱导自愈性皮肤损伤。 IL-12 和 IFN-对于控制感染至关重要。我们感染了 Jun 二聚化蛋白 p21SNFT (Batf3(-/-)) 小鼠（C57BL/6 背景），该小鼠缺乏主要的 IL-12 产生和交叉呈递 CD8(+) 和 CD103(+) DC 亚群。 Batf3(-/-) 小鼠表现出更强的易感性，病变更大，寄生虫负担更高。此外，受感染的 Batf3(-/-) 小鼠引流淋巴结的细胞分泌较少的 IFN-，但分泌更多的 Th2- 和 Th17 型细胞因子，这反映在血清 IgE 和利什曼原虫特异性免疫球蛋白 1 增加（Th2 指示）。重要的是，与CD103(+)DCs相比，从L.major感染小鼠的淋巴结中分离的CD8(+)DCs诱导主要L.major刺激的免疫T细胞分泌更多的IFN-分泌。接下来，我们开发了 CD11c-白喉毒素受体：Batf3(-/-) 混合骨髓嵌合体，以确定 DC 何时对控制感染很重要。从感染后第17天开始消除Batf-3依赖性DC的小鼠或从感染后17-19天开始消除交叉呈递DC的野生型小鼠维持明显更大的病变，类似于从感染开始就消除Batf-3依赖性DC的小鼠。因此，我们已经确定了 Batf-3 依赖性 DC 在针对 L. Major 的防护中发挥着至关重要的作用。
Leishmania major infection induces self-healing cutaneous lesions in C57BL/6 mice. Both IL-12 and IFN- are essential for the control of infection. We infected Jun dimerization protein p21SNFT (Batf3(-/-)) mice (C57BL/6 background) that lack the major IL-12 producing and cross-presenting CD8(+) and CD103(+) DC subsets. Batf3(-/-) mice displayed enhanced susceptibility with larger lesions and higher parasite burden. Additionally, cells from draining lymph nodes of infected Batf3(-/-) mice secreted less IFN-, but more Th2- and Th17-type cytokines, mirrored by increased serum IgE and Leishmania-specific immunoglobulin 1 (Th2 indicating). Importantly, CD8(+) DCs isolated from lymph nodes of L. major-infected mice induced significantly more IFN- secretion by L. major-stimulated immune T cells than CD103(+) DCs. We next developed CD11c-diptheria toxin receptor: Batf3(-/-) mixed bone marrow chimeras to determine when the DCs are important for the control of infection. Mice depleted of Batf-3-dependent DCs from day 17 or wild-type mice depleted of cross-presenting DCs from 17-19 days after infection maintained significantly larger lesions similar to mice whose Batf-3-dependent DCs were depleted from the onset of infection. Thus, we have identified a crucial role for Batf-3-dependent DCs in protection against L. major.