IgA protects resident commensal microbiota against competitors

This week journal Science published new study from Sarkis Mazmanian lab at Caltech describing role of IgA in providing strain-specific competitive advantage to certain resident commensal microbiota. 

His lab has been studying immunobiology of Bacteroides fragilis (B. fragilis), a gut commensal. In initial series of experiments they have compared germ-free mice mono-colonized with either wild-type B. fragilis or its mutant variants such as, Δccf, shown to modify biosynthesis of its capsular polysaccharides. They noticed that in co-housing experiments wild-type B. fragilis from one mouse could out compete mutant variant in another mouse in a horizontal transfer assay.   

Since B. fragilis polysaccharides are known to interact with host's immune system, the authors wanted to find out whether host's immune system influenced co-housing experiments. Not surprisingly, the authors found that mutant B. fragilis did not efficiently bind IgA (induced by wild-type B. fragilis) and that it in turn induced IgA repertoire that bound wild-type B. fragilis even less effectively, suggesting some kind of association between IgA and missing antigens on mutant B. fragilis.  

To verify these observations, the authors compared co-housing experiments between germ-free IgA+ and IgA-KO mice (or treated with B cell depleting antibody) mono-colonized with wild-type B. fragilis. Indeed and surprisingly this time, wild-type B. fragilis resident in IgA KO mice were easily overtaken by wild-type B. fragilis from mono-colonized wild-type mice. These results suggested that in absence of IgA wild-type B. fragilis has lost competitive advantage against wild-type B. fragilis resident in IgA+ mice.

What could these results mean in biological context: it appears that certain resident commensal microbiota benefit from interacting with IgA. The authors proposed that "during health, IgA fosters mucosal colonization of microbiota with beneficial properties....while disease states may induce (or be caused by) IgA responses to pathogens or pathobionts that disrupt healthy microbiome equilibria." This is an interpretation that does not provide clear mechanistic explanation as to how IgA response could make such discrimination at the level of antigens between which microbes to keep and which ones to eject from the host. 

posted by David Usharauli