Parallelism of intestinal secretory IgA shapes functional microbial fitness
Tim Rollenske (),
Sophie Burkhalter,
Lukas Muerner,
Stephan Gunten,
Jolanta Lukasiewicz,
Hedda Wardemann and
Andrew J. Macpherson ()
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Tim Rollenske: University Clinic of Visceral Surgery and Medicine, Inselspital, University of Bern
Sophie Burkhalter: University Clinic of Visceral Surgery and Medicine, Inselspital, University of Bern
Lukas Muerner: University of Bern
Stephan Gunten: University of Bern
Jolanta Lukasiewicz: Ludwik Hirszfeld Institute of Immunology and Experimental Therapy
Hedda Wardemann: German Cancer Research Center
Andrew J. Macpherson: University Clinic of Visceral Surgery and Medicine, Inselspital, University of Bern
Nature, 2021, vol. 598, issue 7882, 657-661
Abstract:
Abstract Dimeric IgA secreted across mucous membranes in response to nonpathogenic taxa of the microbiota accounts for most antibody production in mammals. Diverse binding specificities can be detected within the polyclonal mucosal IgA antibody response1–10, but limited monoclonal hybridomas have been studied to relate antigen specificity or polyreactive binding to functional effects on microbial physiology in vivo11–17. Here we use recombinant dimeric monoclonal IgAs (mIgAs) to finely map the intestinal plasma cell response to microbial colonization with a single microorganism in mice. We identify a range of antigen-specific mIgA molecules targeting defined surface and nonsurface membrane antigens. Secretion of individual dimeric mIgAs targeting different antigens in vivo showed distinct alterations in the function and metabolism of intestinal bacteria, largely through specific binding. Even in cases in which the same microbial antigen is targeted, microbial metabolic alterations differed depending on IgA epitope specificity. By contrast, bacterial surface coating generally reduced motility and limited bile acid toxicity. The overall intestinal IgA response to a single microbe therefore contains parallel components with distinct effects on microbial carbon-source uptake, bacteriophage susceptibility, motility and membrane integrity.
Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:598:y:2021:i:7882:d:10.1038_s41586-021-03973-7
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DOI: 10.1038/s41586-021-03973-7
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