Parallelism of intestinal secretory IgA shapes functional microbial fitness.

Rollenske, Tim; Burkhalter, Sophie; Muerner, Lukas; von Gunten, Stephan; Lukasiewicz, Jolanta; Wardemann, Hedda; Macpherson, Andrew J. (2021). Parallelism of intestinal secretory IgA shapes functional microbial fitness. Nature, 598(7882), pp. 657-661. Springer Nature 10.1038/s41586-021-03973-7

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Gastroenterology
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Pharmacology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Gastroenterologie / Mukosale Immunologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Gastroenterologie / Mukosale Immunologie

UniBE Contributor:

Rollenske, Tim Henning; Burkhalter, Sophie; Mürner, Lukas Dominic; von Gunten, Stephan and Macpherson, Andrew

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1476-4687

Publisher:

Springer Nature

Language:

English

Submitter:

Celine Joray

Date Deposited:

19 Oct 2021 16:18

Last Modified:

30 Oct 2021 00:14

Publisher DOI:

10.1038/s41586-021-03973-7

PubMed ID:

34646015

BORIS DOI:

10.48350/160195

URI:

https://boris.unibe.ch/id/eprint/160195

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