Biological chemistry of immunomodulation by zwitterionic polysaccharides

Capsular polysaccharides isolated from pathogenic bacteria are comprised typically of many repeating units from one to eight or more monosaccharides in length. These polysaccharides stimulate the murine humoral immune system to elicit primarily IgM antibody responses. Studies conducted primarily in the mouse have characterized these polymers as T cell-independent antigens. These mouse studies and the relatively poor immunogenicity of polysaccharides in human hosts have led to the design of vaccines by coupling these polysaccharides to protein carriers to stimulate a T cell-dependent response. However, a newly described class of bacterial polysaccharides has been characterized that have the ability to modulate the cellular immune system. They are structurally diverse, but all share a zwitterionic charge motif that allows them to directly interact with T cells and antigen-presenting cells to initiate an immunomodulatory T cell response. These polymers, termed zwitterionic polysaccharides (ZPSs), elicit T cell-derived chemokines and cytokines that influence the immune response governing at least one classic host response to bacterial infection: abscess formation. This review will describe the biological and structural aspects of ZPSs that convey these activities.