Carbohydrate‐Engineered Neutrophils Modulating Macrophage Phagocytosis and Phenotype

Abstract

The emerging applications of click chemistry for modulating cell surface glycans provide new possibilities for understanding fundamental cellular processes and designing therapeutic tools. Despite success in glycoengineering macrophages among other cell types, less is achieved on the modification of neutrophils, which are at the frontline of innate immune responses but known for short lives. Herein, a two‐step strategy to engineer neutrophil surfaces with carbohydrates is studied. In the first step, the efficiency of three strategies—lipid fusion, chemical conjugation, and metabolic engineering—for adding a clickable chemical group onto the surface of living neutrophils is compared. Having selected lipid fusion as the optimal method, four carbohydrates—glucose, galactose, mannose, and lactose—with corresponding chemical moieties to react with the preplaced clickable chemical group are applied, through a fast‐reacting, mild, click chemical reaction, leading to a rapid modification of the glycans onto the cell membrane. Among all modified and unmodified neutrophils, the ones modified with mannose (Neu‐Man) stimulate macrophage phagocytosis, resulting in increased expression of CD206 and arginase‐1 in the latter cells. The findings suggest an efficient approach to modifying surface glycans on living neutrophils, which may inspire new macrophage‐based anti‐inflammatory therapies.

Keywords

• carbohydrates
• cell membrane engineering
• macrophages
• neutrophils
• phagocytosis