Department of Immunology, University of Connecticut (UConn) Health, Farmington, CT 06030, USA.
Center for Quantitative Medicine, UConn Health, Farmington, CT 06030, USA.
Sci Immunol. 2017 Oct 6;2(16). doi: 10.1126/sciimmunol.aah5520.
The spleen is an important site for generating protective immune responses against pathogens. After infection, immune cells undergo rapid reorganization to initiate and maintain localized inflammatory responses; however, the mechanisms governing this spatial and temporal cellular reorganization remain unclear. We show that the strategic position of splenic marginal zone CD169 macrophages is vital for rapid initiation of antibacterial responses. In addition to controlling initial bacterial growth, CD169 macrophages orchestrate a second phase of innate protection by mediating the transport of bacteria to splenic T cell zones. This compartmentalization of bacteria within the spleen was essential for driving the reorganization of innate immune cells into hierarchical clusters and for local interferon-γ production near sites of bacterial replication foci. Our results show that both phases of the antimicrobial innate immune response were dependent on CD169 macrophages, and, in their absence, the series of events needed for pathogen clearance and subsequent survival of the host was disrupted. Our study provides insight into how lymphoid organ structure and function are related at a fundamental level.
脾脏是产生针对病原体的保护性免疫反应的重要部位。感染后，免疫细胞会迅速重组，以启动和维持局部炎症反应；然而，控制这种空间和时间细胞重组的机制尚不清楚。我们发现，脾脏边缘区 CD169 巨噬细胞的战略位置对于快速启动抗菌反应至关重要。除了控制初始细菌生长外，CD169 巨噬细胞还通过介导细菌向脾脏 T 细胞区的运输来协调先天保护的第二阶段。这种脾脏内细菌的分隔对于驱动固有免疫细胞进入层次化簇的重组以及在细菌复制焦点附近产生局部干扰素-γ是必不可少的。我们的研究结果表明，抗菌先天免疫反应的两个阶段都依赖于 CD169 巨噬细胞，而在没有 CD169 巨噬细胞的情况下，清除病原体和随后宿主存活所需的一系列事件就会被打乱。我们的研究提供了深入了解淋巴器官结构和功能在根本上是如何相关的。
