B cell-intrinsic MyD88 signaling prevents the lethal dissemination of commensal bacteria during colonic damage.
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.
Department of Immunology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA.
Donna
D
Kirkland
Alicia
A
Benson
Julie
J
Mirpuri
Reed
R
Pifer
Baidong
B
Hou
Anthony L
AL
DeFranco
Felix
F
Yarovinsky
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D003106:Colon / Q000187:drug effects / Q000276:immunology* / Q000293:injuries / Q000382:microbiology*; D003165:Complement System Proteins / Q000378:metabolism; D016264:Dextran Sulfate / Q000633:toxicity; D054884:Host-Pathogen Interactions / Q000276:immunology; D007070:Immunoglobulin A / Q000378:metabolism; D007075:Immunoglobulin M / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
D000900:Anti-Bacterial Agents; D007070:Immunoglobulin A; D007075:Immunoglobulin M; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D003165:Complement System Proteins; D016264:Dextran Sulfate