Department of Immunobiology, WHO Collaborative Center for Research and Training in Immunology, University of Lausanne, Epalinges, Switzerland.
Department of Immunobiology, WHO Collaborative Center for Research and Training in Immunology, University of Lausanne, Epalinges, Switzerland.
Cell Rep. 2022 May 3;39(5):110777. doi: 10.1016/j.celrep.2022.110777.
Neutrophils are specialized innate immune cells known for their ability to fight pathogens. However, the mechanisms of neutrophil trafficking to lymph nodes are not fully clear. Using a murine model of dermal infection with Leishmania parasites, we observe a transient neutrophil influx in draining lymph nodes despite sustained recruitment to the infection site. Cell-tracking experiments, together with intravital two-photon microscopy, indicate that neutrophil recruitment to draining lymph nodes occurs minimally through lymphatics from the infected dermis, but mostly through blood vessels via high endothelial venules. Mechanistically, neutrophils do not respond to IL-1β or macrophage-derived molecules. Instead, they are guided by the C5a-C5aR1 axis, using L-selectin and integrins, to extravasate into the draining lymph node parenchyma. We also report that C5, the C5a precursor, is locally produced in the draining lymph node by lymphatic endothelial cells. Our data establish and detail organ-specific mechanisms of neutrophil trafficking.
中性粒细胞是一种专门的先天免疫细胞，以其对抗病原体的能力而闻名。然而，中性粒细胞向淋巴结的迁移机制尚不完全清楚。我们使用一种皮肤感染利什曼原虫的小鼠模型，观察到尽管持续招募到感染部位，但引流淋巴结中存在短暂的中性粒细胞涌入。细胞示踪实验，结合活体双光子显微镜，表明中性粒细胞向引流淋巴结的募集很少通过受感染真皮的淋巴管，而是主要通过血管内皮高通透性小静脉进行。从机制上讲，中性粒细胞不会对白细胞介素-1β或巨噬细胞衍生的分子作出反应。相反，它们通过 C5a-C5aR1 轴，利用 L-选择素和整合素，渗出到引流淋巴结实质中。我们还报告说，C5，C5a 的前体，由引流淋巴结中的淋巴管内皮细胞在局部产生。我们的数据建立并详细描述了中性粒细胞迁移的器官特异性机制。
