Pathway-specific complement activation against Campylobacter jejuni and its role in bacterial killing and neutrophil-mediated clearance

Campylobacter jejuni is a leading cause of bacterial gastroenteritis worldwide, with increasing multidrug resistance making it a significant public health challenge. Although its infections are often self-limiting due to host immunity, complement-mediated bacterial clearance remains underexplored. In this study, we investigated the activation and functional roles of the classical, lectin, and alternative complement pathways against C. jejuni , including multidrug-resistant isolates from human and poultry origins. In vitro analyses showed strong and consistent C3b deposition across all tested strains, highlighting complement activation. C1q binding confirmed the involvement of the classical pathway; however, higher binding of MBL, CL-11, and Factor Bb suggests that the lectin and alternative pathways contribute substantially to complement activation against this pathogen. This activation resulted in effective downstream progression to membrane attack complex (MAC) formation, as evidenced by the deposition of C5b and C9 and strong serum bactericidal activity. Additionally, complement opsonization significantly enhanced neutrophil-mediated bacterial clearance compared with non-opsonized and heat-inactivated serum controls. Overall, our findings indicate that complement-mediated immunity plays an important role in host defence against C. jejuni , with notable contributions from the lectin and alternative pathways. The consistent activation profile across MDR strains highlights complement components as potential targets for adjunct immunotherapeutic strategies.