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Publication : Gut complement induced by the microbiota combats pathogens and spares commensals.

First Author  Wu M Year  2024
Journal  Cell Volume  187
Issue  4 Pages  897-913.e18
PubMed ID  38280374 Mgi Jnum  J:345952
Mgi Id  MGI:7610117 Doi  10.1016/j.cell.2023.12.036
Citation  Wu M, et al. (2024) Gut complement induced by the microbiota combats pathogens and spares commensals. Cell 187(4):897-913.e18
abstractText  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.
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