Histo-blood group antigens as mediators of infections

The critical first step of a microbial infection is usually the attachment of pathogens to host cell glycans. Targets on host tissues are in particular the histo-blood group antigens (HBGAs), which are present in rich diversity in the mucus layer and on the underlying mucosa. Recent structural and functional studies have revealed significant new insight into the molecular mechanisms, explaining why individuals with certain blood groups are at increased risk of some infections. The most prominent example of blood-group-associated diseases is cholera, caused by infection with Vibrio cholerae. Many other microbial pathogens, for example Pseudomonas aeruginosa infecting the airways, and enterotoxigenic Escherichia coli (ETEC) causing traveler's diarrhea, also bind to histo-blood group antigens, but show a less clear correlation with blood group phenotype. Yet other pathogens, for example norovirus and Helicobacter pylori, recognize HBGAs differently depending on the strain. In all cases, milk oligosaccharides can aid the hosts' defenses, acting as natural receptor decoys, and anti-infectious therapy can be designed along similar strategies. In this review, we focus on important infections of humans, but the molecular mechanisms are of general relevance to a broad range of microbial infections of humans and animals.