The One That Got Away: How Macrophage-Derived IL-1β Escapes the Mycolactone-Dependent Sec61 Blockade in Buruli Ulcer.

ABSTRACT: Buruli ulcer (BU), caused by Mycobacterium ulcerans, is a devastating necrotizing skin disease. Key to its pathogenesis is mycolactone, the exotoxin virulence factor that is both immunosuppressive and cytotoxic. The discovery that the essential Sec61 translocon is the major cellular target of mycolactone explains much of the disease pathology, including the immune blockade. Sec61 inhibition leads to a loss in production of nearly all cytokines from monocytes, macrophages, dendritic cells and T cells, as well as antigen presentation pathway proteins and costimulatory molecules. However, there has long been evidence that the immune system is not completely incapable of responding to M. ulcerans infection. In particular, IL-1β was recently shown to be present in BU lesions, and

SUBMITTER: Hall BS 

PROVIDER: S-EPMC8826060 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature