(A) Gut-specific complement expression profile. Complement components involved in the three major activation pathways — classical, lectin, and alternative pathways — are depicted, each converging on C3 activation and leading to effector functions, including opsonization, inflammation, and membrane attack complex (MAC) formation, as in the systemic complement system. However, the intestinal complement system exhibits a locally adapted, restricted expression profile. Indicated expression levels reflect transcriptomic data from the intestine under homeostatic conditions (16): green (three dots) indicates high expression (>100 reads/million), orange (two dots) denotes moderate expression (10–100 reads/million), and red (one dot) represents low expression (<10 reads/million). Intestinal cell types responsible for producing these components are shown in pink rectangles (e.g., stromal cells, myeloid cells, and epithelial cells). (B) Systemic complement function. The liver is the primary source of circulating complement proteins. In the sterile environment of the bloodstream, these proteins support immune defense through opsonization, recruitment of immune cells, phagocytosis, and direct pathogen killing via MAC-mediated lysis. (C) Gut complement function during homeostasis and infection. Under homeostatic conditions (left), C3 is primarily expressed by stromal, myeloid, and epithelial cells in the intestine. Due to limited phagocyte presence and the absence of MAC, this locally produced C3 does not eliminate commensal microbiota. During enteric infection (right), pathogen exposure enhances complement activation, C3 deposition, and promotes neutrophil recruitment and phagocytosis, thereby supporting pathogen clearance.