The gastrointestinal (GI) tract constitutes an essential barrier against ingested microbes, including potential pathogens. Although immune reactions are well studied in the lower GI tract, it remains unclear how adaptive immune responses are initiated during microbial challenge of the oral mucosa (OM), the primary site of microbial encounter in the upper GI tract. Here, we identify mandibular lymph nodes (mandLNs) as sentinel lymphoid organs that intercept ingested Listeria monocytogenes (Lm). Oral Lm uptake led to local activation and release of antigen-specific CD8 + T cells that constituted most of the early circulating effector T cell (T EFF ) pool. MandLN-primed T EFF disseminated to lymphoid organs, lung, and OM and contributed substantially to rapid elimination of target cells. In contrast to CD8 + T EFF generated in mesenteric LN (MLN) during intragastric infection, mandLN-primed T EFF lacked a gut-seeking phenotype, which correlated with low expression of enzymes required for gut-homing imprinting by mandLN stromal and dendritic cells. Accordingly, mandLN-primed T EFF decreased Lm burden in spleen but not MLN after intestinal infection. Our findings extend the concept of regional specialization of immune responses along the length of the GI tract, with CD8 + T EFF generated in the upper GI tract displaying homing profiles that differ from those imprinted by lymphoid tissue of the lower GI tract.

中文翻译：

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口腔黏膜引流淋巴结中的微生物摄取导致缺乏肠道归巢表型的细胞毒性 CD8 + T 细胞快速释放

胃肠道 (GI) 构成了抵御摄入微生物（包括潜在病原体）的重要屏障。尽管在下消化道中对免疫反应进行了很好的研究，但尚不清楚在上消化道微生物接触的主要部位口腔黏膜 (OM) 的微生物攻击期间如何启动适应性免疫反应。在这里，我们将下颌淋巴结 (mandLNs) 识别为拦截摄入的前哨淋巴器官李斯特菌（LM）。口服 Lm 摄取导致抗原特异性 CD8 的局部激活和释放+构成早期循环效应 T 细胞（TEFF） 水池。MandLN引发的TEFF播散到淋巴器官、肺和 OM，并大大促进了靶细胞的快速消除。与 CD8 相比+吨EFF在胃内感染期间在肠系膜 LN (MLN) 中产生，mandLN-primed TEFF缺乏肠道寻找表型，这与 mandLN 基质细胞和树突细胞的肠道归巢印记所需的酶的低表达相关。因此，mandLN-primed TEFF肠道感染后脾脏 Lm 负荷降低，但 MLN 没有降低。我们的研究结果扩展了沿胃肠道长度的免疫反应区域特化的概念，CD8+吨EFF在上消化道产生的归巢分布与下消化道淋巴组织所印记的归巢分布不同。