Mucosal CD8 T Cell Responses Are Shaped by Batf3-DC After Foodborne Listeria monocytogenes Infection.

Mucosal CD8 T Cell Responses Are Shaped by Batf3-DC After Foodborne Listeria monocytogenes Infection.
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DOI:
10.3389/fimmu.2020.575967
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发表时间:
2020
影响因子:
7.3
通讯作者:
Sheridan BS
Sheridan BS
中科院分区:
医学2区
文献类型:
--
作者:
Imperato JN;Xu D;Romagnoli PA;Qiu Z;Perez P;Khairallah C;Pham QM;Andrusaite A;Bravo-Blas A;Milling SWF;Lefrancois L;Khanna KM;Puddington L;Sheridan BS

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虽然免疫反应已被严格检查后,静脉内单核细胞增生李斯特菌(Lm)感染,了解较少,从肠道传播或诱导适应性免疫后,更多的生理模型的食源性感染。因此,本研究集中于肠粘膜和引流肠系膜淋巴结(MLN)中的早期事件,使用经修饰以侵入鼠肠上皮的Lm(InlAM Lm)对小鼠进行食源性感染。InlAM Lm在细胞内从肠运输到MLN,并与结肠中的Batf 3非依赖性树突状细胞(DC)相关。与此一致,InlAM Lm最初通常在Batf 3-/-小鼠中从肠道传播到MLN。活化的迁移性DC在感染后3天在MLN中积累并包围InlAM Lm的病灶。此时,Batf 3-/-小鼠显示出减少的InlAM Lm负荷,暗示cDC 1在MLN中的最大细菌积累中。Batf 3-/-小鼠在InlAM Lm特异性效应CD 8 T细胞的诱导和肠道归巢方面也表现出严重缺陷。病原体负荷的恢复没有拯救Batf 3-/-小鼠中的抗原特异性CD 8 T细胞应答,表明Batf 3在食源性感染后产生抗InlAM Lm免疫中的关键作用。总的来说,这些数据表明,DC在食源性InlAM Lm感染后的早期事件中以及在驱动肠道Lm特异性效应T细胞的建立中发挥不同的动态作用。
While immune responses have been rigorously examined after intravenous Listeria monocytogenes (Lm) infection, less is understood about its dissemination from the intestines or the induction of adaptive immunity after more physiologic models of foodborne infection. Consequently, this study focused on early events in the intestinal mucosa and draining mesenteric lymph nodes (MLN) using foodborne infection of mice with Lm modified to invade murine intestinal epithelium (InlAM Lm). InlAM Lm trafficked intracellularly from the intestines to the MLN and were associated with Batf3-independent dendritic cells (DC) in the lymphatics. Consistent with this, InlAM Lm initially disseminated from the gut to the MLN normally in Batf3–/– mice. Activated migratory DC accumulated in the MLN by 3 days post-infection and surrounded foci of InlAM Lm. At this time Batf3–/– mice displayed reduced InlAM Lm burdens, implicating cDC1 in maximal bacterial accumulation in the MLN. Batf3–/– mice also exhibited profound defects in the induction and gut-homing of InlAM Lm-specific effector CD8 T cells. Restoration of pathogen burden did not rescue antigen-specific CD8 T cell responses in Batf3–/– mice, indicating a critical role for Batf3 in generating anti-InlAM Lm immunity following foodborne infection. Collectively, these data suggest that DC play diverse, dynamic roles in the early events following foodborne InlAM Lm infection and in driving the establishment of intestinal Lm-specific effector T cells.
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