Mycolactone suppresses T cell responsiveness by altering both early signaling and posttranslational events. - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Journal of Immunology Année : 2010

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

Résumé

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.

Dates et versions

pasteur-00594632 , version 1 (24-09-2020)

Identifiants

Citer

Sheerazed Boulkroun, Laure Guenin-Macé, Maria-Isabel Thoulouze, Marc Monot, Anaïs Merckx, et al.. Mycolactone suppresses T cell responsiveness by altering both early signaling and posttranslational events.. Journal of Immunology, 2010, 184 (3), pp.1436-44. ⟨10.4049/jimmunol.0902854⟩. ⟨pasteur-00594632⟩
65 Consultations
8 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More