Evaluation of the bactericidal activity of galectins

Abstract

Over a century ago, Karl Landsteiner discovered that blood group antigens could predict the immunological outcome of red blood cell transfusion. While the discovery of ABO(H) blood group antigens revolutionized transfusion medicine, many questions remain regarding the development and regulation of naturally occurring anti-blood group antibody formation. Early studies suggested that blood group antibodies develop following stimulation by bacteria that express blood group antigens. While this may explain the development of anti-blood group antibodies in blood group negative individuals, how blood group positive individuals, who cannot generate anti-blood group antibodies, protect themselves against blood group positive microbes remained unknown. Recent studies suggest that several members of the galectin family specifically target blood group positive microbes, thereby providing innate immune protection against blood group antigen positive microbes regardless of the blood group status of an individual. Importantly, subsequent studies suggest that this unique form of immunity may not be limited to blood group expressing microbes, but may reflect a more generalized form of innate immunity against molecular mimicry. As this form of antimicrobial activity represents a unique and unprecedented form of immunity, we will examine important considerations and methodological approaches that can be used when seeking to ascertain the potential antimicrobial activity of various members of the galectin family.

Figure 1. Galectins provide innate immunity against blood group positive microbes

While elimination of self-reactive immune cells reduces the probability of autoimmunity, a fitness cost would be anticipated due to the reduced ability of an individual to respond to self-like antigens on pathogens. However, compensatory mechanisms at the level of innate immunity may exist whereby individuals protect themselves against self-like antigens. Gal-4 and Gal-8 uniquely recognize pathogens baring self-antigens, providing a possible mechanism whereby individuals protect themselves against self-antigen positive pathogens despite reduced adaptive immunity toward these microbes.

Figure 2. Galectin-4 and Galectin-8 killing blood group positive microbes requires carbohydrate recognition

Quantification of viable bacteria after BGB⁺ E. coli were mixed with 5 μM Gal-1, Gal-3, Gal-4 or Gal-8 (A), 5 μM Gal-4 with or without 20 mM lactose (Lac) or 20 mM sucrose (Sucr.) (B), 5 μM Gal-8 with or without 20 mM lactose (Lac) or 20 mM sucrose (Sucr.) (D) or the indicated concentrations of Gal-1, Gal-3, Gal-4 and Gal-8 (D). In each experiment, bacteria were quantified by dilution plating. Error bars represent means ± s.d. This research was originally published in Nature Medicine. Stowell SR, Arthur CM, Dias-Baruffi M, Rodrigues LC, Gourdine JP, Heimburg-Molinaro J, Ju T, Molinaro RJ, Rivera-Marrero C, Xia B, Smith DF, Cummings RD. Innate immune lectins kill bacteria expressing blood group antigen. 2010 Mar;16(3):295–301