Inflammasome-triggered IL-18 controls skin inflammation in the progression of Buruli ulcer

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dc.contributor.authorSuzuki, T.
dc.contributor.authorBoonyaleka, K.
dc.contributor.authorAblordey, A.S.
dc.contributor.authoret al.
dc.date.accessioned2024-01-17T20:11:55Z
dc.date.available2024-01-17T20:11:55Z
dc.date.issued2023
dc.descriptionResearch Articleen_US
dc.description.abstractBuruli ulcer is an emerging chronic infectious skin disease caused by Mycobacterium ulcerans. Mycolactone, an exotoxin produced by the bacterium, is the only identified virulence factor so far, but the functions of this toxin and the mechanisms of disease progression remain unclear. By interfering with the Sec61 translocon, mycolactone inhibits the Sec61-dependent co-translational translocation of newly synthesized proteins, such as induced cytokines and immune cell receptors into the endoplasmic reticulum. However, in regard to IL-1β, which is Secreted by a Sec61-independent mechanism, mycolactone has been shown to induce IL-1β secretion via activation of inflammasomes. In this study, we clarified that cytokine induction, including that of IL-1β, in infected macrophages was suppressed by mycolactone produced by M. ulcerans subsp. shinshuense, despite the activation of caspase-1 through the Inflammasome activation is triggered in a manner independent of mycolactone. Intriguingly, mycolactone suppressed the expression of proIL-1β as well as TNF-α at the transcriptional level, suggesting that mycolactone of M. ulcerans subsp. shinshuense may exert additional inhibitory effect on proIL-1β expression. Remarkably, constitutively produced IL-18 was cleaved and mature IL-18 was actually released from macrophages infected with the causative mycobacterium. IL-18-deficient mice infected subcutaneously with M. ulcerans experienced exacerbated skin inflammation during the course of disease progression. On the other On the other hand, IL-1β controls bacterial multiplication in skin tissues. These results provide information regarding the mechanisms and functions of the induced cytokines in the pathology of Buruli ulcer.en_US
dc.identifier.otherhttps://doi.org/10.1371/journal.ppat.1011747
dc.identifier.urihttp://ugspace.ug.edu.gh:8080/handle/123456789/41099
dc.language.isoenen_US
dc.publisherPLOS Pathogensen_US
dc.subjectBuruli ulceren_US
dc.subjectskin inflammationen_US
dc.subjectprogressionen_US
dc.titleInflammasome-triggered IL-18 controls skin inflammation in the progression of Buruli ulceren_US
dc.typeArticleen_US

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