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

Area of Science:

• Immunology
• Microbiology
• Gastroenterology

Background:

• The complement system's role in the bloodstream is well-established for pathogen clearance.
• Its function on intestinal mucosal surfaces remains less understood.
• Local complement activity is crucial for maintaining gut homeostasis.

Purpose of the Study:

• To investigate the local synthesis and function of complement component 3 (C3) in the gut.
• To determine the relationship between gut microbiota, C3 levels, and host defense against enteric pathogens.
• To elucidate the mechanisms by which the gut complement system differentiates between commensals and pathogens.

Main Methods:

• Quantification of C3 expression in gut stromal cells.
• Analysis of C3 regulation by microbiota composition in humans and mice.
• Assessment of the impact of C3 levels on protection against enteric infection.
• Investigation of membrane attack complex (MAC) component presence in the gut.

Main Results:

• Complement component 3 (C3) is synthesized locally in the gut, primarily by stromal cells.
• C3 expression is induced by commensal colonization and modulated by microbiota composition.
• Gut C3 levels correlate directly with protection against enteric infections.
• The absence of MAC components prevents commensal lysis, allowing C3 deposition.

Conclusions:

• The gut possesses a unique complement system that acts as an innate immune sentinel.
• Local C3 production defends against pathogens while tolerating commensal bacteria.
• Microbiota composition shapes individual host C3 levels and infection susceptibility.