Gut microbiota utilize immunoglobulin A for mucosal colonization.

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PubMed ID: 29724905

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Donaldson GP, Ladinsky MS, Yu KB, Sanders JG, Yoo BB, Chou WC, Conner ME, Earl AM, Knight R, Bjorkman PJ, Mazmanian SK

Science. 05 2018. doi: 10.1126/science.aaq0926

COMMENT: Experiments in mice suggest that Bacteroides fragilis change its surface to faciliate the binding of IgA. It facilitates adherence to gut mucosa in vivo. The authors propose that IgA mediated responses are involved in the stablishment of host-microbial symbiosis in the gut.

IgA is the main antibody isotype secreted in the gut. It shapes the gut microbiome and several grams of IgA are daily produced.

The authors used transmission electron microscopy to analyze the Bacteroides fragilis interaction with gut mucosa:

we used transmission electron microscopy (TEM) to visualize colonic tissues of monocolonized mice. B. fragilis  commonly formed discrete aggregates of tightly-packed cells on the apical epithelial surface and penetrated the glycocalyx layer of transmembrane mucins, nearly contacting the microvilli. Intact B. fragilis  cells were also found nestled in the ducts of the crypts of Lieberkühn.

The authors previously had identified a genetic locus in B. fragilis (ccfABCDE) necessary for colonization of colonic crypts. In this work they got to monocolonize mice with a ccfCDE  (Δccf ) mutant. Using TEM they observed that the mutant bacteria were excluded from the glycocalyx and they do not form aggregates as wild-type bacteria. A thick, fuzzy capsule layer covering wild-type B. fragilis was very reduced in the mutant. After exhaustive experiments the authors concluded that the CCF system regulates capsule expression and mediates B. fragilis  mucosal colonization. After that they tested whether capsular polysaccharide regulation by ccf affected IgA recognition of bacteria and yes, they discovered that wild type B. fragilis was highly coated with IgA, which was significantly diminished in Δccf  and in mutants for the polysaccharides B and C. It is curious that in this case the capsular polysaccharides are useful for the bacteria for immune atracction to stablish a simbiotic mucosal colonization instead of being useful for immne evasion as in other cases of pathogenic bacteria.

The authors suggest  a link between IgA deficiency and autoimmune disease via microbiome and suggest a different impact of IgA in healthy and in disease states: 

Mucosal microbiome instability or loss of immunomodulatory species may underlie the link between IgA deficiency and autoimmune diseases in humans.

We propose 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. Indeed, computational models indicate that IgA can both maintain indigenous mucosal populations  and clear invasive pathogens. In addition to serving as a defense system, we discover that adaptive immunity evolved to engender intimate association with members of the gut microbiome.



Raquel Tobes