B Cell-Intrinsic MyD88 Signaling Prevents the Lethal Dissemination of Commensal Bacteria during Colonic Damage

Donna Kirkland, Alicia Benson, Julie Mirpuri, Reed Pifer, Baidong Hou, Anthony L. DeFranco, Felix Yarovinsky

Research output: Contribution to journalArticle

77 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)228-238
Number of pages11
JournalImmunity
Volume36
Issue number2
DOIs
StatePublished - Feb 24 2012

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Dextran Sulfate
B-Lymphocytes
Bacteria
Myeloid Differentiation Factor 88
Toll-Like Receptors
Immunoglobulin M
Mammals
Homeostasis
Anti-Bacterial Agents
Mortality

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases
  • Immunology

Cite this

B Cell-Intrinsic MyD88 Signaling Prevents the Lethal Dissemination of Commensal Bacteria during Colonic Damage. / Kirkland, Donna; Benson, Alicia; Mirpuri, Julie; Pifer, Reed; Hou, Baidong; DeFranco, Anthony L.; Yarovinsky, Felix.

In: Immunity, Vol. 36, No. 2, 24.02.2012, p. 228-238.

Research output: Contribution to journalArticle

Kirkland, Donna ; Benson, Alicia ; Mirpuri, Julie ; Pifer, Reed ; Hou, Baidong ; DeFranco, Anthony L. ; Yarovinsky, Felix. / B Cell-Intrinsic MyD88 Signaling Prevents the Lethal Dissemination of Commensal Bacteria during Colonic Damage. In: Immunity. 2012 ; Vol. 36, No. 2. pp. 228-238.
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