Source:http://linkedlifedata.com/resource/pubmed/id/20042571
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
3
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| pubmed:dateCreated |
2010-1-21
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| pubmed:abstractText |
Mycolactone is a diffusible lipid toxin produced by Mycobacterium ulcerans, the causative agent of a necrotizing skin disease referred to as Buruli ulcer. Intriguingly, patients with progressive lesions display a systemic suppression of Th1 responses that resolves on surgical excision of infected tissues. In this study, we examined the effects of mycolactone on the functional biology of T cells and identified two mechanisms by which mycolactone suppresses cell responsiveness to antigenic stimulation. At noncytotoxic concentrations, mycolactone blocked the activation-induced production of cytokines by a posttranscriptional, mammalian target of rapamycin, and cellular stress-independent mechanism. In addition, mycolactone triggered the lipid-raft association and activation of the Src-family kinase, Lck. Mycolactone-mediated hyperactivation of Lck resulted in the depletion of intracellular calcium stores and downregulation of the TCR, leading to impaired T cell responsiveness to stimulation. These biochemical alterations were not observed when T cells were exposed to other bacterial lipids, or to structurally related immunosuppressors. Mycolactone thus constitutes a novel type of T cell immunosuppressive agent, the potent activity of which may explain the defective cellular responses in Buruli ulcer patients.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
AIM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Feb
|
| pubmed:issn |
1550-6606
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:day |
1
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| pubmed:volume |
184
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
1436-44
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| pubmed:meshHeading |
pubmed-meshheading:20042571-Animals,
pubmed-meshheading:20042571-Bacterial Toxins,
pubmed-meshheading:20042571-Buruli Ulcer,
pubmed-meshheading:20042571-Cells, Cultured,
pubmed-meshheading:20042571-Humans,
pubmed-meshheading:20042571-Immunity, Cellular,
pubmed-meshheading:20042571-Immunosuppressive Agents,
pubmed-meshheading:20042571-Intracellular Fluid,
pubmed-meshheading:20042571-Jurkat Cells,
pubmed-meshheading:20042571-Lymphocyte Activation,
pubmed-meshheading:20042571-Lymphocyte Specific Protein Tyrosine Kinase p56(lck),
pubmed-meshheading:20042571-Mice,
pubmed-meshheading:20042571-Mice, Inbred C57BL,
pubmed-meshheading:20042571-Mycobacterium ulcerans,
pubmed-meshheading:20042571-Protein Processing, Post-Translational,
pubmed-meshheading:20042571-Signal Transduction,
pubmed-meshheading:20042571-T-Lymphocytes,
pubmed-meshheading:20042571-Time Factors
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| pubmed:year |
2010
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| pubmed:articleTitle |
Mycolactone suppresses T cell responsiveness by altering both early signaling and posttranslational events.
|
| pubmed:affiliation |
Unité Postulante Pathogénomique Mycobactérienne Intégrée, Institut Pasteur, Paris, France.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
|