Linked Life Data

17979981

Source:http://linkedlifedata.com/resource/pubmed/id/17979981

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2008-2-8
pubmed:abstractText
Myeloid differentiation factor (MyD)88, an adaptor protein shared by the Toll-interleukin 1 receptor superfamily, plays a critical role in host defence during many systemic bacterial infections by inducing protective inflammatory responses that limit bacterial growth. However, the role of innate responses during gastrointestinal (GI) infections is less clear, in part because the GI tract is tolerant to commensal antigens. The current study investigated the role of MyD88 following infection by the murine bacterial pathogen, Citrobacter rodentium. MyD88-deficient mice suffered a lethal colitis coincident with colonic mucosal ulcerations and bleeding. Their susceptibility was associated with an overwhelming bacterial burden and selectively impaired immune responses in colonic tissues, which included delayed inflammatory cell recruitment, reduced iNOS and abrogated production of TNF-alpha and IL-6 from MyD88-deficient macrophages and colons cultured ex vivo. Immunostaining for Ki67 and BrDU revealed that MyD88 signalling mediated epithelial hyper-proliferation in response to C. rodentium infection. Thus, MyD88-deficient mice could not promote epithelial cell turnover and repair, leading to deep bacterial invasion of colonic crypts, intestinal barrier dysfunction and, ultimately, widespread mucosal ulcerations. In conclusion, MyD88 signalling within the GI tract plays a critical role in mediating host defence against an enteric bacterial pathogen, by controlling bacterial numbers and promoting intestinal epithelial homeostasis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1462-5822
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
10
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
618-31
pubmed:meshHeading
pubmed-meshheading:17979981-Animals, pubmed-meshheading:17979981-Bone Marrow, pubmed-meshheading:17979981-Citrobacter rodentium, pubmed-meshheading:17979981-Colitis, pubmed-meshheading:17979981-Colon, pubmed-meshheading:17979981-Colony Count, Microbial, pubmed-meshheading:17979981-Enzyme-Linked Immunosorbent Assay, pubmed-meshheading:17979981-Epithelial Cells, pubmed-meshheading:17979981-Interleukin-6, pubmed-meshheading:17979981-Ki-67 Antigen, pubmed-meshheading:17979981-Macrophages, pubmed-meshheading:17979981-Mice, pubmed-meshheading:17979981-Mice, Inbred C57BL, pubmed-meshheading:17979981-Mice, Knockout, pubmed-meshheading:17979981-Myeloid Differentiation Factor 88, pubmed-meshheading:17979981-Nitric Oxide Synthase Type II, pubmed-meshheading:17979981-Organ Culture Techniques, pubmed-meshheading:17979981-Survival Analysis, pubmed-meshheading:17979981-Tumor Necrosis Factor-alpha
pubmed:year
2008
pubmed:articleTitle
MyD88 signalling plays a critical role in host defence by controlling pathogen burden and promoting epithelial cell homeostasis during Citrobacter rodentium-induced colitis.
pubmed:affiliation
Division of Gastroenterology, BC Children's Hospital, University of British Columbia, Vancouver, British Columbia, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't