Department of Experimental Immunology.
Department of Molecular Infection Biology.
J Infect Dis. 2017 Sep 15;216(6):752-760. doi: 10.1093/infdis/jix037.
To successfully limit pathogen dissemination, an immunological link between the entry tissue of the pathogen and the underlying secondary lymphoid organs (SLOs) needs to be established to prime adaptive immune responses. Here, the prerequisite of CCR7 to mount host immune responses within SLOs during gastrointestinal Yersinia pseudotuberculosis infection to limit pathogen spread was investigated.
Survival, bacterial dissemination, and intestinal and systemic pathology of wild-type and CCR7-/- mice were assessed and correlated to the presence of immune cell subsets and cytokine responses throughout the course of infection.
The CCR7-/- mice show a significantly higher morbidity and are more prone to pathogen dissemination and intestinal and systemic inflammation during the oral route of infection. Significant impact of CCR7 deficiency over the course of infection on several immunological parameters were observed (ie, elevated neutrophil-dominated innate immune response in Peyer's patches, limited dendritic cell migration to mesenteric lymph nodes [mLNs] causing reduced T cell-mediated adaptive immune responses (in particular Th17-like responses) in mLNs).
Our work indicates that CCR7 is required to mount a robust immune response against enteropathogenic Y. pseudotuberculosis by promoting Th17-like responses in mLNs.
为了成功限制病原体的传播，病原体进入组织与潜在的次级淋巴器官（SLO）之间需要建立免疫联系，以启动适应性免疫反应。在这里，研究了 CCR7 在胃肠道假结核耶尔森菌感染期间在 SLO 内引发宿主免疫反应以限制病原体传播的前提条件。
评估了野生型和 CCR7-/-小鼠的存活率、细菌传播以及肠道和系统性病理学，并将其与感染过程中免疫细胞亚群和细胞因子反应的存在相关联。
CCR7-/-小鼠在口服感染途径中表现出更高的发病率，更易发生病原体传播和肠道及系统性炎症。在感染过程中，CCR7 缺陷对多个免疫学参数产生了显著影响（例如，派尔集合淋巴结中嗜中性粒细胞主导的先天免疫反应增加，树突状细胞向肠系膜淋巴结的迁移受限，导致 mLN 中的 T 细胞介导的适应性免疫反应（特别是 Th17 样反应）减少）。
我们的工作表明，CCR7 通过促进 mLN 中的 Th17 样反应，对肠道致病性假结核耶尔森菌引发强大的免疫反应是必需的。
