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Gut microbiota utilize immunoglobulin A for mucosal colonization

Donaldson, G. P. and Ladinsky, M. S. and Yu, K. B. and Sanders, J. G. and Yoo, B. B. and Chou, W.-C. and Conner, M. E. and Earl, A. M. and Knight, R. and Bjorkman, P. J. and Mazmanian, S. K. (2018) Gut microbiota utilize immunoglobulin A for mucosal colonization. Science, 360 (6390). pp. 795-800. ISSN 0036-8075. http://resolver.caltech.edu/CaltechAUTHORS:20180327-133708907

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Abstract

The immune system responds vigorously to microbial infection while permitting lifelong colonization by the microbiome. Mechanisms that facilitate the establishment and stability of the gut microbiota remain poorly described. We found that a regulatory system in the prominent human commensal Bacteroides fragilis modulates its surface architecture to invite binding of immunoglobulin A (IgA) in mice. Specific immune recognition facilitated bacterial adherence to cultured intestinal epithelial cells and intimate association with the gut mucosal surface in vivo. The IgA response was required for B. fragilis (and other commensal species) to occupy a defined mucosal niche that mediates stable colonization of the gut through exclusion of exogenous competitors. Therefore, in addition to its role in pathogen clearance, we propose that IgA responses can be co-opted by the microbiome to engender robust host-microbial symbiosis.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1126/science.aaq0926DOIArticle
https://www.sciencemag.org/content/360/6390/795/suppl/DC1PublisherSupplementary Materials
ORCID:
AuthorORCID
Bjorkman, P. J.0000-0002-2277-3990
Mazmanian, S. K.0000-0003-2713-1513
Additional Information:© 2018 American Association for the Advancement of Science. Received 29 September 2017; accepted 29 March 2018. Published online 3 May 2018. We thank E. Hsiao, J. Round, H. Chu, and members of the Mazmanian laboratory for critical review of this manuscript. The anti-CD20 antibody was provided under an MTA from Genentech. IgA−/− mice were originally generated at Baylor College of Medicine, and an MTA was required to obtain them. We thank T. Thron, the Caltech Office of Laboratory Animal Resources, Caltech Genomics Laboratory, and Caltech Flow Cytometry Facility for technical support. Funding: Supported by NIH training grant 5T32 GM07616 and NSF Graduate Research Fellowship DGE-1144469 (G.P.D.), NIH grant U19AI110818 to the Broad Institute,NIH grants P50 GM082545 and AI04123 (P.J.B.), and NIH grants GM099535 and DK083633 and the Heritage Medical Research Institute (S.K.M.). Author contributions: G.P.D. and S.K.M. conceived the study and designed experiments; G.P.D. performed most of the experiments; M.S.L. performed electron microscopy; K.B.Y. and B.B.Y. performed mouse and tissue culture experiments; J.G.S. analyzed 16S sequencing data; W.C.C. analyzed RNA-seq data; S.K.M., P.J.B., R.K., A.M.E., and M.E.C. supervised research and provided guidance on analysis and interpretations; G.P.D. and S.K.M. wrote the paper; and all authors edited the manuscript. Competing interests: The authors declare no competing interests. Data and materials availability: All data and code to understand and assess the conclusions of this research are available in the main text and supplementary materials, as well as EMBL-EBI accession ERP107727 and NCBI Bioproject accessions PRJNA445716 and PRJNA438372.
Group:Heritage Medical Research Institute
Funders:
Funding AgencyGrant Number
NIH Predoctoral Fellowship5T32 GM07616
NSF Graduate Research FellowshipDGE-1144469
NIHU19AI110818
NIHP50 GM082545
NIHAI04123
NIHGM099535
NIHDK083633
Heritage Medical Research InstituteUNSPECIFIED
Record Number:CaltechAUTHORS:20180327-133708907
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20180327-133708907
Official Citation:Gut microbiota utilize immunoglobulin A for mucosal colonization. BY G. P. DONALDSON, M. S. LADINSKY, K. B. YU, J. G. SANDERS, B. B. YOO, W.-C. CHOU, M. E. CONNER, A. M. EARL, R. KNIGHT, P. J. BJORKMAN, S. K. MAZMANIAN. SCIENCE 18 MAY 2018: 795-800.
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:85463
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:05 Apr 2018 20:43
Last Modified:18 May 2018 16:36

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