Portimine A toxin causes skin inflammation through ZAKα-dependent NLRP1 inflammasome activation.
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PubMed
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| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | Artículo científico |
| Lenguaje: | en |
| Publicado: |
EMBO molecular medicine
2025
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| author | Gorse, Léana Plessis, Loïc Wearne, Stephen Paradis, Margaux Pinilla, Miriam Chua, Rae Lim, Seong Soo Pelluz, Elena Toh, Gee-Ann Mazars, Raoul Bomfim, Caio Hervé, Fabienne Lhaute, Korian Réveillon, Damien Suire, Bastien Ravon-Katossky, Léa Benoist, Thomas Fromont, Léa Péricat, David Neil Mertens, Kenneth Derrien, Amélie Terre-Terrillon, Aouregan Chomérat, Nicolas Bilien, Gwenaël Séchet, Véronique Carpentier, Liliane Fall, Mamadou Sonko, Amidou Hakim, Hadi Sadio, Nfally Bourdeaux, Jessie Cougoule, Céline Henras, Anthony K Perez-Oliva, Ana Belen Brehmer, Patrice Roca, Francisco J Zhong, Franklin L Common, John Meunier, Etienne Hess, Philipp |
| author_facet | Gorse, Léana Plessis, Loïc Wearne, Stephen Paradis, Margaux Pinilla, Miriam Chua, Rae Lim, Seong Soo Pelluz, Elena Toh, Gee-Ann Mazars, Raoul Bomfim, Caio Hervé, Fabienne Lhaute, Korian Réveillon, Damien Suire, Bastien Ravon-Katossky, Léa Benoist, Thomas Fromont, Léa Péricat, David Neil Mertens, Kenneth Derrien, Amélie Terre-Terrillon, Aouregan Chomérat, Nicolas Bilien, Gwenaël Séchet, Véronique Carpentier, Liliane Fall, Mamadou Sonko, Amidou Hakim, Hadi Sadio, Nfally Bourdeaux, Jessie Cougoule, Céline Henras, Anthony K Perez-Oliva, Ana Belen Brehmer, Patrice Roca, Francisco J Zhong, Franklin L Common, John Meunier, Etienne Hess, Philipp Gorse, Léana Plessis, Loïc Wearne, Stephen Paradis, Margaux Pinilla, Miriam Chua, Rae Lim, Seong Soo Pelluz, Elena Toh, Gee-Ann Mazars, Raoul Bomfim, Caio Hervé, Fabienne Lhaute, Korian Réveillon, Damien Suire, Bastien Ravon-Katossky, Léa Benoist, Thomas Fromont, Léa Péricat, David Neil Mertens, Kenneth Derrien, Amélie Terre-Terrillon, Aouregan Chomérat, Nicolas Bilien, Gwenaël Séchet, Véronique Carpentier, Liliane Fall, Mamadou Sonko, Amidou Hakim, Hadi Sadio, Nfally Bourdeaux, Jessie Cougoule, Céline Henras, Anthony K Perez-Oliva, Ana Belen Brehmer, Patrice Roca, Francisco J Zhong, Franklin L Common, John Meunier, Etienne Hess, Philipp |
| collection | PubMed - marine biology |
| contents | Portimine A toxin causes skin inflammation through ZAKα-dependent NLRP1 inflammasome activation. Gorse, Léana Plessis, Loïc Wearne, Stephen Paradis, Margaux Pinilla, Miriam Chua, Rae Lim, Seong Soo Pelluz, Elena Toh, Gee-Ann Mazars, Raoul Bomfim, Caio Hervé, Fabienne Lhaute, Korian Réveillon, Damien Suire, Bastien Ravon-Katossky, Léa Benoist, Thomas Fromont, Léa Péricat, David Neil Mertens, Kenneth Derrien, Amélie Terre-Terrillon, Aouregan Chomérat, Nicolas Bilien, Gwenaël Séchet, Véronique Carpentier, Liliane Fall, Mamadou Sonko, Amidou Hakim, Hadi Sadio, Nfally Bourdeaux, Jessie Cougoule, Céline Henras, Anthony K Perez-Oliva, Ana Belen Brehmer, Patrice Roca, Francisco J Zhong, Franklin L Common, John Meunier, Etienne Hess, Philipp Humans Animals Inflammasomes Zebrafish Keratinocytes Marine Toxins Skin Dinoflagellida NLR Proteins Dermatitis Inflammation 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 ZAKα and P38 and promotes the nucleation of the human NLRP1 inflammasome, leading to the release of IL-1β/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 ZAKα-NLRP1 axis drives skin necrosis and inflammation. Our results exemplify the threats to human health caused by emerging environmental toxins and identify ZAKα and NRLP1 as important pharmacological targets to mitigate PortimineA toxicity. |
| format | Artículo científico |
| id | pubmed_39948420 |
| institution | PubMed |
| language | en |
| publishDate | 2025 |
| publisher | EMBO molecular medicine |
| record_format | pubmed |
| spellingShingle | Portimine A toxin causes skin inflammation through ZAKα-dependent NLRP1 inflammasome activation. Gorse, Léana Plessis, Loïc Wearne, Stephen Paradis, Margaux Pinilla, Miriam Chua, Rae Lim, Seong Soo Pelluz, Elena Toh, Gee-Ann Mazars, Raoul Bomfim, Caio Hervé, Fabienne Lhaute, Korian Réveillon, Damien Suire, Bastien Ravon-Katossky, Léa Benoist, Thomas Fromont, Léa Péricat, David Neil Mertens, Kenneth Derrien, Amélie Terre-Terrillon, Aouregan Chomérat, Nicolas Bilien, Gwenaël Séchet, Véronique Carpentier, Liliane Fall, Mamadou Sonko, Amidou Hakim, Hadi Sadio, Nfally Bourdeaux, Jessie Cougoule, Céline Henras, Anthony K Perez-Oliva, Ana Belen Brehmer, Patrice Roca, Francisco J Zhong, Franklin L Common, John Meunier, Etienne Hess, Philipp Humans Animals Inflammasomes Zebrafish Keratinocytes Marine Toxins Skin Dinoflagellida NLR Proteins Dermatitis Inflammation Portimine A toxin causes skin inflammation through ZAKα-dependent NLRP1 inflammasome activation. Gorse, Léana Plessis, Loïc Wearne, Stephen Paradis, Margaux Pinilla, Miriam Chua, Rae Lim, Seong Soo Pelluz, Elena Toh, Gee-Ann Mazars, Raoul Bomfim, Caio Hervé, Fabienne Lhaute, Korian Réveillon, Damien Suire, Bastien Ravon-Katossky, Léa Benoist, Thomas Fromont, Léa Péricat, David Neil Mertens, Kenneth Derrien, Amélie Terre-Terrillon, Aouregan Chomérat, Nicolas Bilien, Gwenaël Séchet, Véronique Carpentier, Liliane Fall, Mamadou Sonko, Amidou Hakim, Hadi Sadio, Nfally Bourdeaux, Jessie Cougoule, Céline Henras, Anthony K Perez-Oliva, Ana Belen Brehmer, Patrice Roca, Francisco J Zhong, Franklin L Common, John Meunier, Etienne Hess, Philipp Humans Animals Inflammasomes Zebrafish Keratinocytes Marine Toxins Skin Dinoflagellida NLR Proteins Dermatitis Inflammation 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 ZAKα and P38 and promotes the nucleation of the human NLRP1 inflammasome, leading to the release of IL-1β/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 ZAKα-NLRP1 axis drives skin necrosis and inflammation. Our results exemplify the threats to human health caused by emerging environmental toxins and identify ZAKα and NRLP1 as important pharmacological targets to mitigate PortimineA toxicity. |
| title | Portimine A toxin causes skin inflammation through ZAKα-dependent NLRP1 inflammasome activation. |
| topic | Humans Animals Inflammasomes Zebrafish Keratinocytes Marine Toxins Skin Dinoflagellida NLR Proteins Dermatitis Inflammation |
| url | https://pubmed.ncbi.nlm.nih.gov/39948420/ |