Galectin‐3 binds Neisseria meningitidis and increases interaction with phagocytic cells

Summary Galectin‐3 is expressed and secreted by immune cells and has been implicated in multiple aspects of the inflammatory response. It is a glycan binding protein which can exert its functions within cells or exogenously by binding cell surface ligands, acting as a molecular bridge or activating signalling pathways. In addition, this lectin has been shown to bind to microorganisms. In this study we investigated the interaction between galectin‐3 and Neisseria meningitidis, an important extracellular human pathogen, which is a leading cause of septicaemia and meningitis. Immunohistochemical analysis indicated that galectin‐3 is expressed during meningococcal disease and colocalizes with bacterial colonies in infected tissues from patients. We show that galectin‐3 binds to N. meningitidis and we demonstrate that this interaction requiresfull‐length, intact lipopolysaccharide molecules. We found that neither exogenous nor endogenous galectin‐3 contributes to phagocytosis of N. meningitidis; instead exogenous galectin‐3 increases adhesion to monocytes and macrophages but not epithelial cells. Finally we used galectin‐3 deficient (Gal‐3−/−) mice to evaluate the contribution of galectin‐3 to meningococcal bacteraemia. We found that Gal‐3−/− mice had significantly lower levels of bacteraemia compared with wild‐type mice after challenge with live bacteria, indicating that galectin‐3 confers an advantage to N. meningitidis during systemic infection. Galectins are beta‐galactoside binding lectins which are implicated in several fundamental biological processes including development, adhesion and modulation of immune responses. In this study, we show that galectin‐3 is expressed during meningococcal infection and can bind to the lipopolysaccharide molecules of Neisseria meningitidis, enhancing the adhesion of the pathogen to macrophages. Furthermore, we demonstrate that galectin‐3 promotes bacteraemia, suggesting that the meningococcus can exploit this lectin to enhance survival in the host.