Department of Immunology, University of Toronto, Toronto, ON, Canada.
Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada.
Sci Immunol. 2023 Aug 4;8(86):eabq4573. doi: 10.1126/sciimmunol.abq4573.
Maintaining macrophage (MΦ) heterogeneity is critical to ensure intestinal tissue homeostasis and host defense. The gut microbiota and host factors are thought to synergistically guide intestinal MΦ development, although the exact nature, regulation, and location of such collaboration remain unclear. Here, we report that microbial biochemical energy metabolism promotes colony-stimulating factor 2 (CSF2) production by group 3 innate lymphoid cells (ILC3s) within solitary isolated lymphoid tissues (SILTs) in a cell-extrinsic, NLRP3/P2X7R-dependent fashion in the steady state. Tissue-infiltrating monocytes accumulating around SILTs followed a spatially constrained, distinct developmental trajectory into SILT-associated MΦs (SAMs). CSF2 regulated the mitochondrial membrane potential and reactive oxygen species production of SAMs and contributed to the antimicrobial defense against enteric bacterial infections. Collectively, these findings identify SILTs and CSF2-producing ILC3s as a microanatomic niche for intestinal MΦ development and functional programming fueled by the integration of commensal microbial energy metabolism.
维持巨噬细胞（MΦ）的异质性对于确保肠道组织的稳态和宿主防御至关重要。肠道微生物群和宿主因素被认为协同指导肠道 MΦ 的发育，尽管这种协同作用的确切性质、调节和位置仍不清楚。在这里，我们报告称，微生物生化能量代谢以细胞外在、NLRP3/P2X7R 依赖的方式促进固有淋巴细胞 3（ILC3）在孤立的淋巴滤泡组织（SILTs）中产生集落刺激因子 2（CSF2），在稳态下。在 SILTs 周围积累的组织浸润单核细胞遵循空间受限的、独特的发育轨迹进入与 SILT 相关的巨噬细胞（SAMs）。CSF2 调节 SAM 的线粒体膜电位和活性氧的产生，并有助于对抗肠道细菌感染的抗菌防御。总的来说，这些发现确定了 SILTs 和产生 CSF2 的 ILC3s 作为肠道 MΦ 发育和功能编程的微观解剖龛，其动力来自共生微生物能量代谢的整合。
