Gut complement induced by the microbiota combats pathogens and spares commensals
Publication information:
Meng Wu, Wen Zheng, Xinyang Song, Bin Bao, Yuanyou Wang, Deepshika Ramanan, Daping Yang, Rui Liu, John Macbeth, Elyza Do, Warrison Andrade, Tiandi Yang, Hyoung-Soo Cho, Francesca Gazzaniga, Marit Ilves, Daniela Coronado, Charlotte Thompson, Saiyu Hang, Isaac Chiu, Jeffrey Moffitt, Ansel Hsiao, John Mekalanos, Christophe Benoist, and Dennis Kasper. 2024. “Gut Complement Induced by the Microbiota Combats Pathogens and Spares Commensals”. Cell, 187, 4, Pp. 897-913.e18. doi:10.1016/j.cell.2023.12.036
Abstract
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.