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Bacteria-Killing Proteins Address Immune Blind Spot to Blood Type Antigens

A set of proteins found in the human intestine can recognize and kill bacteria that have human blood group antigens on their surfaces, according to collaborating scientists from the Emory University School of Medicine in the United States and the University of Sao Paulo in Brazil. "It's like having a platoon in an army whose sole purpose is to track down enemy soldiers that are wearing the home country's uniforms,” said Emory’s Dr. Richard Cummings, senior author of the report. The potential problem is that the human body’s adaptive immunity system, as a self-protective mechanism, eliminates any of its immune cells that recognize the body’s own blood group antigen type (A, AB, or B). That means that the adaptive immune system is potentially vulnerable to attack by bacteria that express a human blood group antigen on their surfaces. The scientists investigated how humans cope with this potentially dangerous vulnerability. Emory graduate students Connie Arthur and Dr. Sean Sowell identified two particular intestinal proteins (galectin-4 and galectin-8) that kill strains of E. coli that express human blood group antigens on their surfaces. The proteins do not kill E. coli strains that do not express these antigens on their surfaces. The researches further found that the killing activity of both galectin-4 and galectin-8 is mediated by their C-terminal domains, occurs rapidly, takes place independently of complement, and is accompanied by disruption of membrane integrity. "These proteins are separate from antibodies and other parts of the immune system," Dr. Cummings said. "They kill bacteria like E. coli O86 all by themselves within a couple of minutes." The E. coli O86 strain has molecules on its surface like those in humans with blood type B. The galectin proteins did not kill human red blood cells expressing blood group antigens. This research work was reported online on February 14, 2010 in Nature Medicine. [Press release] [Nature Medicine abstract]