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An Immunomodulatory Molecule of Symbiotic Bacteria Directs Maturation of the Host Immune System

Mazmanian, Sarkis K. and Liu, Cui Hua and Tzianabos, Arthur O. and Kasper, Dennis L. (2005) An Immunomodulatory Molecule of Symbiotic Bacteria Directs Maturation of the Host Immune System. Cell, 122 (1). pp. 107-118. ISSN 0092-8674. https://resolver.caltech.edu/CaltechAUTHORS:20200309-164447119

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Abstract

The mammalian gastrointestinal tract harbors a complex ecosystem consisting of countless bacteria in homeostasis with the host immune system. Shaped by evolution, this partnership has potential for symbiotic benefit. However, the identities of bacterial molecules mediating symbiosis remain undefined. Here we show that, during colonization of animals with the ubiquitous gut microorganism Bacteroides fragilis, a bacterial polysaccharide (PSA) directs the cellular and physical maturation of the developing immune system. Comparison with germ-free animals reveals that the immunomodulatory activities of PSA during B. fragilis colonization include correcting systemic T cell deficiencies and T_H1/T_H2 imbalances and directing lymphoid organogenesis. A PSA mutant of B. fragilis does not restore these immunologic functions. PSA presented by intestinal dendritic cells activates CD4⁺ T cells and elicits appropriate cytokine production. These findings provide a molecular basis for host-bacterial symbiosis and reveal the archetypal molecule of commensal bacteria that mediates development of the host immune system.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1016/j.cell.2005.05.007DOIArticle
ORCID:
AuthorORCID
Mazmanian, Sarkis K.0000-0003-2713-1513
Additional Information:© 2005 Elsevier Under an Elsevier user license. Received 12 January 2005, Revised 28 February 2005, Accepted 4 May 2005, Available online 14 July 2005. We thank Drs. A. Onderdonk, R. Cisneros, and R.T. Bronson for expert technical and intellectual contributions; Drs. M. Wessels, C. Nagler-Anderson, L. Comstock, J. McCoy, and H. Ton-That for critical reviews of the manuscript; and members of the Kasper and Tzianabos labs for assistance throughout the work. This study was supported by a WHO Fellowship to C.H.L. (WPRO 0003/03) and a Postdoctoral Fellowship from the Helen Hay Whitney Foundation to S.K.M. This work was supported by funding from the NIH (NIH/NIAID R01AI039576) to D.L.K.
Funders:
Funding AgencyGrant Number
World Health OrganizationWPRO 0003/03
Helen Hay Whitney FoundationUNSPECIFIED
NIHR01AI039576
Issue or Number:1
Record Number:CaltechAUTHORS:20200309-164447119
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20200309-164447119
Official Citation:Sarkis K. Mazmanian, Cui Hua Liu, Arthur O. Tzianabos, Dennis L. Kasper, An Immunomodulatory Molecule of Symbiotic Bacteria Directs Maturation of the Host Immune System, Cell, Volume 122, Issue 1, 2005, Pages 107-118, ISSN 0092-8674, https://doi.org/10.1016/j.cell.2005.05.007.
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:101804
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:10 Mar 2020 14:36
Last Modified:10 Mar 2020 14:36

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