Calvin, Phoebe and Joan Snyder Institute for Chronic Diseases, University of Calgary, Alberta T2N 4N1, Canada.
Department of Microbiology and Immunology, Center for Immunology, University of Minnesota, Minneapolis, MN 55455.
J Immunol. 2020 May 1;204(9):2552-2561. doi: 10.4049/jimmunol.2000022. Epub 2020 Mar 23.
The adaptive immune function of lymph nodes is dependent on constant recirculation of lymphocytes. In this article, we identify neutrophils present in the lymph node at steady state, exhibiting the same capacity for recirculation. In germ-free mice, neutrophils still recirculate through lymph nodes, and in mice cohoused with wild microbiome mice, the level of neutrophils in lymph nodes increases significantly. We found that at steady state, neutrophils enter the lymph node entirely via L-selectin and actively exit via efferent lymphatics via an S1P dependent mechanism. The small population of neutrophils in the lymph node can act as reconnaissance cells to recruit additional neutrophils in the event of bacterial dissemination to the lymph node. Without these reconnaissance cells, there is a delay in neutrophil recruitment to the lymph node and a reduction in swarm formation following infection. This ability to recruit additional neutrophils by lymph node neutrophils is initiated by LTB4. This study establishes the capacity of neutrophils to recirculate, much like lymphocytes via L-selectin and high endothelial venules in lymph nodes and demonstrates how the presence of neutrophils at steady state fortifies the lymph node in case of an infection disseminating through lymphatics.
淋巴结的适应性免疫功能依赖于淋巴细胞的持续再循环。在本文中,我们发现了在稳态下存在于淋巴结中的中性粒细胞,它们同样具有再循环的能力。在无菌小鼠中,中性粒细胞仍然通过淋巴结再循环,而在与野生微生物组小鼠共栖的小鼠中,淋巴结中的中性粒细胞水平显著增加。我们发现,在稳态下,中性粒细胞完全通过 L 选择素进入淋巴结,并通过 S1P 依赖的机制通过输出淋巴管主动离开。淋巴结中少量的中性粒细胞可以作为侦察细胞,在细菌扩散到淋巴结时招募更多的中性粒细胞。如果没有这些侦察细胞,中性粒细胞向淋巴结的募集就会延迟,感染后 swarm 的形成也会减少。淋巴结中性粒细胞通过 LTB4 来启动招募额外中性粒细胞的能力。本研究确立了中性粒细胞像淋巴细胞一样通过 L 选择素和淋巴结中的高内皮静脉再循环的能力,并展示了在通过淋巴管传播的感染情况下,稳态下中性粒细胞的存在如何增强淋巴结的功能。