Differential Recognition of Lipopolysaccharide O-Antigens by the Pattern Recognition Molecules MBL and Ficolins of...

The complement system plays a crucial role in bridging innate and adaptive immune responses. When activated, a proteolytic cascade leads to pathogen destruction. It is initiated via the recognition of foreign structures by three pathways: the classical, the lectin, and the alternative. This study focuses on the lectin pathway and the role of four pattern recognition molecules (PRMs), mannan-binding lectin, H-ficolin, L-ficolin, and M-ficolin, in the recognition of microbial patterns and the initiation of complement activation. These PRMs bind to specific carbohydrate structures; each PRM has unique ligand specificities. We investigated the PRM interactions with lipopolysaccharide (LPS) of Gram-negative bacteria.

Utilizing a microarray of 120 distinct LPS structures, the study aims to map the diversity of PRM-LPS interactions and assess their role in complement activation.

Our findings reveal that all four PRMs preferentially bind to the O-antigens of LPS, rather than lipid A or the core oligosaccharide, contradicting previous suggestions. Each PRM displayed distinct binding patterns to different LPS structures, although some overlaps were observed. These interactions were partially confirmed with whole bacteria. MBL binding to E. coli O30 and O126, as well as H-ficolin binding to E. coli O108 led to complement activation on the bacterial surface.

The application of a wide array of LPS structures expands and clarifies the spectrum of bacterial glycoconjugates that interact with PRMs, known to activate the complement system.