Skip to Main content Skip to Navigation
Journal articles

Mycolactone toxin induces an inflammatory response by targeting the IL-1β pathway: Mechanistic insight into Buruli ulcer pathophysiology

Abstract : Mycolactone, a lipid-like toxin, is the major virulence factor of Mycobacterium ulcerans, the etiological agent of Buruli ulcer. Its involvement in lesion development has been widely described in early stages of the disease, through its cytotoxic and immunosuppressive activities, but less is known about later stages. Here, we revisit the role of mycolactone in disease outcome and provide the first demonstration of the pro-inflammatory potential of this toxin. We found that the mycolactone-containing mycobacterial extracellular vesicles produced by M. ulcerans induced the production of IL-1β, a potent pro-inflammatory cytokine, in a TLR2dependent manner, targeting NLRP3/1 inflammasomes. We show our data to be relevant in a physiological context. The in vivo injection of these mycolactone-containing vesicles induced a strong local inflammatory response and tissue damage, which were prevented by corticosteroids. Finally, several soluble pro-inflammatory factors, including IL-1β, were detected in infected tissues from mice and Buruli ulcer patients. Our results revisit Buruli ulcer pathophysiology by providing new insight, thus paving the way for the development of new therapeutic strategies taking the pro-inflammatory potential of mycolactone into account.
Complete list of metadatas

https://www.hal.inserm.fr/inserm-03113905
Contributor : Nathalie Labarriere <>
Submitted on : Monday, January 18, 2021 - 4:20:47 PM
Last modification on : Wednesday, January 27, 2021 - 12:32:02 PM

File

Foulon et al 2020 ppat.pdf
Publisher files allowed on an open archive

Identifiers

Citation

M Foulon, M Robbe-Saule, J Manry, L Esnault, Y Boucaud, et al.. Mycolactone toxin induces an inflammatory response by targeting the IL-1β pathway: Mechanistic insight into Buruli ulcer pathophysiology. PLoS Pathogens, Public Library of Science, 2020, 16 (12), pp.e1009107. ⟨10.1371/journal.ppat.1009107⟩. ⟨inserm-03113905⟩

Share

Metrics

Record views

103

Files downloads

100