School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom.
J Infect Dis. 2014 Jun 1;209(11):1847-56. doi: 10.1093/infdis/jit819. Epub 2013 Dec 26.
The mucosal immune system must initiate and regulate protective immunity, while balancing this immunity with tolerance to harmless antigens and bacterial commensals. We have explored the hypothesis that mucosal dendritic cells (DC) control the balance between regulation and immunity, by studying the responses of human tonsil-derived DC to Neisseria meningitidis as a model organism. We show that tonsil DC are able to sample their antigenic environment, internalizing Nm and expressing high levels of HLA-DR and CD86. However, in comparison to monocyte-derived DC (moDC), they respond to pathogen encounter with only low level cytokine production, largely dominated by TGFβ. Functionally, tonsil DC also only stimulated low levels of antigen-specific T cell proliferation and cytokine production when compared to moDC. We therefore propose that the default role for DC in the nasopharynx is to maintain tolerance/ignorance of the large volume of harmless antigens and bacterial commensals encountered at the nasopharyngeal mucosa.
黏膜免疫系统必须启动和调节保护性免疫，同时使这种免疫与对无害抗原和共生细菌的耐受性相平衡。我们通过研究人类扁桃体衍生树突状细胞（DC）对脑膜炎奈瑟菌（Nm）的反应，探索了黏膜 DC 控制调节和免疫之间平衡的假说，Nm 被作为一种模式生物。我们发现扁桃体 DC 能够对其抗原环境进行采样，内化 Nm 并表达高水平的 HLA-DR 和 CD86。然而，与单核细胞衍生的 DC（moDC）相比，它们对病原体的反应仅产生低水平的细胞因子，主要由 TGFβ 主导。在功能上，与 moDC 相比，扁桃体 DC 也仅刺激低水平的抗原特异性 T 细胞增殖和细胞因子产生。因此，我们提出，DC 在鼻咽部的默认作用是维持对鼻咽黏膜上遇到的大量无害抗原和共生细菌的耐受/忽视。
