Research Highlights

Bacteria: Bloody disguise foiled

Mary O'Reilly

Humans and some primates express variations of three types of carbohydrate antigens on their red blood cells that allow for classification by A, B or O(H) blood group. People with blood type A express the blood group A antigen. Since they lack the B blood group antigen, these individuals also express anti-B antibodies, but not anti-A antibodies that would recognize 'self' antigen. AB blood types have both antigens and no antibodies directed against blood group carbohydrates A, B or O(H), whereas people with blood type O lack these antigens altogether and generate antibodies against both A and B carbohydrates.

This complex adaptive immune response to blood groups antigens creates a gap in immunity. Some bacteria have evolved to take advantage of the lack of antibody production in some individuals by synthesizing blood group antigen carbohydrates in their cell walls. Given that the immune system cannot generate antibodies against those bacteria without harming “self” cells, the bacteria gain an edge in their quest to colonize. Writing in Nature Medicine, Richard Cummings and colleagues describe a back-up immune detection mechanism in which two members of the galectin family of glycan-binding proteins recognize and kill bacteria disguised with blood group antigens.

Given that they lack antibodies directed against the blood group B antigen, people with blood type B or AB are more susceptible to a certain type of Escherichia coli bacteria that express the B-type epitope than are those with blood type A or O. Hypothesizing that there might be some other immune mechanism to recognize blood group carbohydrates on these and other bacteria in the absence of an antibody response, the authors sifted through glycan array screening data available from the Consortium for Functional Glycomics. From this, they discovered that galectin-4 and galectin-8 – but not all galectins – have unusual and novel specificity for human blood group A and B antigens.

Next, the authors wondered whether galectin–blood-group interactions have a biological role in the context of bacterial infection. Not only did they find that galectin-4 and galectin-8 bind to blood group B-positive (BGB⁺) E. coli, but they were also surprised to discover that these galectins kill the bacteria by disrupting membrane integrity. These galectins did not bind bacteria lacking blood group B (BGB– bacteria), indicating that galectin killing was specific to one blood group carbohydrate. When mice were fed both BGB⁺ and BGB⁻ E. coli, the number of BGB⁻ bacteria later recovered was significantly higher than the number of BGB⁺ bacteria. Thus, by rendering E. coli more susceptible to galectin killing, blood group B antigen expression impaired bacterial survival in this model.

Galectins are highly expressed in the intestinal mucosa, where they are perfectly poised to defend against pathogens such as E. coli. This study suggests that by recognizing blood group antigens, galectins-4 and-8 may have evolved into innate immune sentinels capable of wiping out gut bacteria that might otherwise escape detection.

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Buschman, H. (2010) B cells: Siglecs stop self-attack
Buschman, H. (2009) Molecular mimicry: Sugar coating bacterial infection

Author: Heather Buschman