Gorse L., Plessis L., Wearne S., Paradis M., Pinilla M., Chua R., Lim S. S., Pelluz E., Toh G. A., Mazars R., Bomfim C., Hervé F., Lhaute K., Réveillon D., Suire B., Ravon-Katossky L., Benoist T., Fromont L., Péricat D., Mertens K. N., Derrien A., Terre-Terrillon A., Chomérat N., Bilien G., Séchet V., Carpentier L., Fall M., Sonko A., Hakim H., Sadio N., Bourdeaux J., Cougoule C., Henras A. K., Perez-Oliva A. B., Brehmer Patrice, Roca F. J., Zhong F. L., Common J., Meunier E., Hess P. (2025). Portimine A toxin causes skin inflammation through ZAK A-dependent NLRP1 inflammasome activation. EMBO Molecular Medicine, [Early access], p. [28 p.]. ISSN 1757-4676.
Titre du document
Portimine A toxin causes skin inflammation through ZAK A-dependent NLRP1 inflammasome activation
Année de publication
2025
Auteurs
Gorse L., Plessis L., Wearne S., Paradis M., Pinilla M., Chua R., Lim S. S., Pelluz E., Toh G. A., Mazars R., Bomfim C., Hervé F., Lhaute K., Réveillon D., Suire B., Ravon-Katossky L., Benoist T., Fromont L., Péricat D., Mertens K. N., Derrien A., Terre-Terrillon A., Chomérat N., Bilien G., Séchet V., Carpentier L., Fall M., Sonko A., Hakim H., Sadio N., Bourdeaux J., Cougoule C., Henras A. K., Perez-Oliva A. B., Brehmer Patrice, Roca F. J., Zhong F. L., Common J., Meunier E., Hess P.
Source
EMBO Molecular Medicine, 2025,
[Early access], p. [28 p.] ISSN 1757-4676
In 2020-2021, a "mysterious illness" struck Senegalese fishermen, causing severe acute dermatitis in over one thousand individuals following exposure through drift-net fishing activity. Here, by performing deep analysis of the environmental samples we reveal the presence of the marine dinoflagellate Vulcanodinium rugosum and its associated cyclic imine toxins. Specifically, we show that the toxin PortimineA, strongly enriched in environmental samples, impedes ribosome function in human keratinocytes, which subsequently activates the stress kinases ZAK alpha and P38 and promotes the nucleation of the human NLRP1 inflammasome, leading to the release of IL-1 beta/IL-18 pro-inflammatory cytokines and cell death. Furthermore, cell-based models highlight that naturally occurring mutations in the P38-targeted sites of human NLRP1 are unable to respond to PortimineA exposure. Finally, the development and use of human organotypic skins and zebrafish models of PortimineA exposure demonstrate that the ZAK alpha-NLRP1 axis drives skin necrosis and inflammation. Our results exemplify the threats to human health caused by emerging environmental toxins and identify ZAK alpha and NRLP1 as important pharmacological targets to mitigate PortimineA toxicity.
Plan de classement
Sciences fondamentales / Techniques d'analyse et de recherche [020]
;
Limnologie biologique / Océanographie biologique [034]
;
Santé : généralités [050]
Localisation
Fonds IRD [F B010092782]
Identifiant IRD
fdi:010092782
