Blood type and the microbiome- untangling a complex relationship with lessons from pathogens
Graphical abstract
Section snippets
ABCs of ABO
At the beginning of the 20th century Dr. Karl Landsteiner discovered the ABO blood group, which not only informed safe blood transfusions but profoundly contributed to our understanding of the human immune system [1]. Over a century later there are 36 recognized blood groups but the ABO/H, secretor and Lewis systems remain the most clinically relevant and are known together as the histo-blood group antigens (HBGA) [2,3]. An individual’s blood type can be defined by two factors: 1) specific
Attachment and adherence
For many microbes, success in the host begins with the ability to adhere, and host glycans are ideal receptors. The diversity of blood glycan structures likely arose as a means to inhibit the binding of pathogens to host cells, but these molecules also present a scaffold for commensals [21,22,6]. It has been proposed that the secretion of these glycans also evolved as a strategy to bind up pathogens before they encounter infectable cells [23]. These evolutionary skirmishes have resulted in
Masquerading and mimicry
Once anchored in the host, a microbe needs to avoid detection and clearance. An effective tactic to evade host immune responses is directly co-opting or mimicking host antigens [30]. A particularly nefarious strategy employed by Group A Streptococcus is to lyse host red blood cells and then cloak themselves in the erythrocyte membrane to evade detection by circulating immune cells [31••]. A more refined strategy is to express molecules that mimic host glycans [32]. For instance, E. coli O86
Farmers and foragers
Bacteria not only target HBGAs as receptors but can utilize them as a nutrient source. Some bacteria even have the capacity to induce host expression of these glycans. The infant gut is dominated by sialylated glycans and the mature gut is defined by fucosylated glycans including the ABO blood antigens. This shift to fucosylated glycans, like the induction of anti-ABO antibodies, is dependent on colonization of the gut by microbes [47]. The induction of glycan expression is of direct benefit to
Quandaries and questions
The relationships between bacteria and host blood glycans are abundant and complex. The very existence of different blood types is likely the result of millennia of evolutionary arms races and peace treaties between microbes and mammals. While these relationships and the mechanisms driving them have been well explored in culturable strains of bacteria, they remain relatively unexamined with our commensal bacteria.
Although multiple studies have found that secretor status is significantly
Funding sources
This work was supported by the National Institutes of Health NIAID training grant (Training Program in Immunology; T32-AI07405) award to Kathleen L Arnolds.
Conflict of interest statement
Nothing declared.
References and recommended reading
Papers of particular interest, published within the period of review, have been highlighted as:
• of special interest
•• of outstanding interest
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