Department of Immunology, Harvard Medical School, Boston, MA 02115, USA.
Division of Gastroenterology, Boston Children's Hospital, and Harvard Medical School, Boston, MA 02115, USA.
Cell. 2024 Feb 15;187(4):897-913.e18. doi: 10.1016/j.cell.2023.12.036. Epub 2024 Jan 26.
Canonically, the complement system is known for its rapid response to remove microbes in the bloodstream. However, relatively little is known about a functioning complement system on intestinal mucosal surfaces. Herein, we report the local synthesis of complement component 3 (C3) in the gut, primarily by stromal cells. C3 is expressed upon commensal colonization and is regulated by the composition of the microbiota in healthy humans and mice, leading to an individual host's specific luminal C3 levels. The absence of membrane attack complex (MAC) components in the gut ensures that C3 deposition does not result in the lysis of commensals. Pathogen infection triggers the immune system to recruit neutrophils to the infection site for pathogen clearance. Basal C3 levels directly correlate with protection against enteric infection. Our study reveals the gut complement system as an innate immune mechanism acting as a vigilant sentinel that combats pathogens and spares commensals.
从规范上讲，补体系统以其快速清除血流中微生物的能力而闻名。然而，人们对肠道黏膜表面补体系统的功能知之甚少。在此，我们报告了肠道中补体成分 3（C3）的局部合成，主要由基质细胞合成。C3 在共生定植时表达，并受健康人类和小鼠微生物群组成的调节，导致个体宿主特定的腔内腔 C3 水平。肠道中缺乏膜攻击复合物（MAC）成分可确保 C3 沉积不会导致共生菌的裂解。病原体感染会触发免疫系统招募中性粒细胞到感染部位以清除病原体。基础 C3 水平与预防肠道感染直接相关。我们的研究揭示了肠道补体系统作为一种先天免疫机制，作为一种警惕的哨兵，对抗病原体并保护共生菌。
