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© Research
Publication : Journal of immunology (Baltimore, Md. : 1950)

Mycolactone suppresses T cell responsiveness by altering both early signaling and posttranslational events

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Journal of immunology (Baltimore, Md. : 1950) - 30 Dec 2009

Boulkroun S, Guenin-Macé L, Thoulouze MI, Monot M, Merckx A, Langsley G, Bismuth G, Di Bartolo V, Demangel C

Link to Pubmed [PMID] – 20042571

J. Immunol. 2010 Feb;184(3):1436-44

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.

https://www.ncbi.nlm.nih.gov/pubmed/20042571

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