McMaster Immunology Research Centre, M.G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario L8S 4K1, Canada; and Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario L8S 4K1, Canada.
McMaster Immunology Research Centre, M.G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario L8S 4K1, Canada; and Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario L8S 4K1, Canada
J Immunol. 2018 Mar 1;200(5):1746-1760. doi: 10.4049/jimmunol.1701109. Epub 2018 Jan 26.
, the pathogen causing pulmonary tuberculosis (TB) in humans, has evolved to delay Th1 immunity in the lung. Although conventional dendritic cells (cDCs) are known to be critical to the initiation of T cell immunity, the differential roles and molecular mechanisms of migratory CD11b and CD103 cDC subsets in anti- Th1 activation remain unclear. Using a murine model of pulmonary infection, we found that slow arrival of -bearing migratory CD11b and CD103 cDCs at the draining lymph nodes preceded the much-delayed Th1 immunity and protection in the lung. Contrary to their previously described general roles in Th polarization, CD11b cDCs, but not CD103 cDCs, were critically required for Th1 activation in draining lymph nodes following infection. CD103 cDCs counterregulated CD11b cDC-mediated Th1 activation directly by producing the immune-suppressive cytokine IL-10. Thus, our study provides new mechanistic insights into differential Th immune regulation by migratory cDC subsets and helps to develop novel vaccines and therapies.
结核分枝杆菌（Mycobacterium tuberculosis），导致人类肺结核（TB）的病原体，已经进化到在肺部延迟 Th1 免疫。虽然众所周知，传统树突状细胞（conventional dendritic cells，cDCs）对于启动 T 细胞免疫至关重要，但在抗 Th1 激活方面，迁移性 CD11b 和 CD103 cDC 亚群的差异作用和分子机制仍不清楚。我们使用肺部感染的小鼠模型发现，携带抗原的迁移性 CD11b 和 CD103 cDC 缓慢到达引流淋巴结，先于肺部 Th1 免疫和保护作用的明显延迟。与它们先前在 Th 极化中的一般作用相反，在感染后，CD11b cDCs 而不是 CD103 cDCs 对于引流淋巴结中的 Th1 激活是至关重要的。CD103 cDCs 通过产生免疫抑制细胞因子 IL-10 直接对 CD11b cDC 介导的 Th1 激活进行负调控。因此，我们的研究为迁移性 cDC 亚群对 Th 免疫的差异调节提供了新的机制见解，并有助于开发新的疫苗和治疗方法。
