Service interruption on Monday 11 July from 12:30 to 13:00: all the sites of the CCSD (HAL, EpiSciences, SciencesConf, AureHAL) will be inaccessible (network hardware connection).
Skip to Main content Skip to Navigation
Journal articles

Immunity against Mycobacterium ulcerans - The subversive role of mycolactone

Abstract : Mycobacterium ulcerans causes Buruli ulcer, a neglected tropical skin disease manifesting as chronic wounds that can leave victims with major, life-long deformity and disability. Differently from other mycobacterial pathogens, M. ulcerans produces mycolactone, a diffusible lipid factor with unique cytotoxic and immunomodulatory properties. Both traits result from mycolactone targeting Sec61, the entry point of the secretory pathway in eukaryotic cells. By inhibiting Sec61, mycolactone prevents the host cell’s production of secreted proteins, and most of its transmembrane proteins. This molecular blockade dramatically alters the functions of immune cells, thereby the generation of protective immunity. Moreover, sustained inhibition of Sec61 triggers proteotoxic stress responses leading to apoptotic cell death, which can stimulate vigorous immune responses. The dynamics of bacterial production of mycolactone and elimination by infected hosts thus critically determine the balance between its immuno-stimulatory and -suppressive effects. Following an introduction summarizing the essential information on Buruli ulcer disease, this review focuses on the current state of knowledge regarding mycolactone’s regulation and biodistribution. We then detail the consequences of mycolactone-mediated Sec61 blockade on initiation and maintenance of innate and adaptive immune responses. Finally, we discuss the key questions to address in order to improve immunity to M. ulcerans, and how increased knowledge of mycolactone biology may pave the way to innovative therapeutics.
Document type :
Journal articles
Complete list of metadata
Contributor : Marie-Luce Kop Connect in order to contact the contributor
Submitted on : Wednesday, June 2, 2021 - 4:14:08 PM
Last modification on : Tuesday, April 19, 2022 - 11:48:01 AM
Long-term archiving on: : Friday, September 3, 2021 - 7:44:34 PM


CD_PMID 33607704.pdf
Files produced by the author(s)


Distributed under a Creative Commons Attribution - NoDerivatives 4.0 International License




Caroline Demangel. Immunity against Mycobacterium ulcerans - The subversive role of mycolactone. Immunological Reviews, Wiley, 2021, 301 (1), pp.209-221. ⟨10.1111/imr.12956⟩. ⟨pasteur-03246855⟩



Record views


Files downloads