TY - JOUR
T1 - B Cell-Intrinsic MyD88 Signaling Prevents the Lethal Dissemination of Commensal Bacteria during Colonic Damage
AU - Kirkland, Donna
AU - Benson, Alicia
AU - Mirpuri, Julie
AU - Pifer, Reed
AU - Hou, Baidong
AU - DeFranco, Anthony L.
AU - Yarovinsky, Felix
N1 - Funding Information:
This research was supported by NIH R01 AI085263 to F.Y. and P01AI078869 to A.L.D. We thank D. Rakheja and J. Shelton for their help with the histology and pathology scoring.
PY - 2012/2/24
Y1 - 2012/2/24
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84857444508&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84857444508&partnerID=8YFLogxK
U2 - 10.1016/j.immuni.2011.11.019
DO - 10.1016/j.immuni.2011.11.019
M3 - Article
C2 - 22306056
AN - SCOPUS:84857444508
SN - 1074-7613
VL - 36
SP - 228
EP - 238
JO - Immunity
JF - Immunity
IS - 2
ER -