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Immunity. 2012 Feb 24;36(2):228-38. doi: 10.1016/j.immuni.2011.11.019. Epub 2012 Feb 1.

B cell-intrinsic MyD88 signaling prevents the lethal dissemination of commensal bacteria during colonic damage.

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  • 1Department of Immunology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA.

Abstract

The Toll-like receptor adaptor protein MyD88 is essential for the regulation of intestinal homeostasis in mammals. In this study, we determined that Myd88-deficient mice are susceptible to colonic damage that is induced by dextran sulfate sodium (DSS) administration resulting from uncontrolled dissemination of intestinal commensal bacteria. The DSS-induced mortality of Myd88-deficient mice was completely prevented by antibiotic treatment to deplete commensal bacteria. By using cell type-specific Myd88-deficient mice, we established that B cell-intrinsic MyD88 signaling plays a central role in the resistance to DSS-induced colonic damage via the production of IgM and complement-mediated control of intestinal bacteria. Our results indicate that the lack of intact MyD88 signaling in B cells, coupled with impaired epithelial integrity, enables commensal bacteria to function as highly pathogenic organisms, causing rapid host death.

Copyright © 2012 Elsevier Inc. All rights reserved.

PMID:
22306056
[PubMed - indexed for MEDLINE]
PMCID:
PMC3288553
Free PMC Article

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