RIPK1 activates distinct gasdermins in macrophages and neutrophils upon pathogen blockade of innate immune signaling.

Détails

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Accès restreint UNIL
Etat: Public
Version: Final published version
Licence: Non spécifiée
ID Serval
serval:BIB_595417C2F004
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
RIPK1 activates distinct gasdermins in macrophages and neutrophils upon pathogen blockade of innate immune signaling.
Périodique
Proceedings of the National Academy of Sciences of the United States of America
Auteur⸱e⸱s
Chen K.W., Demarco B., Ramos S., Heilig R., Goris M., Grayczyk J.P., Assenmacher C.A., Radaelli E., Joannas L.D., Henao-Mejia J., Tacchini-Cottier F., Brodsky I.E., Broz P.
ISSN
1091-6490 (Electronic)
ISSN-L
0027-8424
Statut éditorial
Publié
Date de publication
13/07/2021
Peer-reviewed
Oui
Volume
118
Numéro
28
Pages
34260403
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
Injection of effector proteins to block host innate immune signaling is a common strategy used by many pathogenic organisms to establish an infection. For example, pathogenic Yersinia species inject the acetyltransferase YopJ into target cells to inhibit NF-κB and MAPK signaling. To counteract this, detection of YopJ activity in myeloid cells promotes the assembly of a RIPK1-caspase-8 death-inducing platform that confers antibacterial defense. While recent studies revealed that caspase-8 cleaves the pore-forming protein gasdermin D to trigger pyroptosis in macrophages, whether RIPK1 activates additional substrates downstream of caspase-8 to promote host defense is unclear. Here, we report that the related gasdermin family member gasdermin E (GSDME) is activated upon detection of YopJ activity in a RIPK1 kinase-dependent manner. Specifically, GSDME promotes neutrophil pyroptosis and IL-1β release, which is critical for anti-Yersinia defense. During in vivo infection, IL-1β neutralization increases bacterial burden in wild-type but not Gsdme-deficient mice. Thus, our study establishes GSDME as an important mediator that counteracts pathogen blockade of innate immune signaling.
Mots-clé
3T3 Cells, Animals, Cytokines/metabolism, Host-Pathogen Interactions/immunology, Immunity, Innate, Interleukin-1beta/metabolism, Macrophages/metabolism, Mice, Mice, Inbred C57BL, Neoplasm Proteins/metabolism, Neutrophils/metabolism, Pyroptosis, Receptor-Interacting Protein Serine-Threonine Kinases/metabolism, Signal Transduction, Yersinia pseudotuberculosis/physiology, Yersinia pseudotuberculosis Infections/immunology, Yersinia pseudotuberculosis Infections/microbiology, RIPK1, Yersinia, caspases, gasdermin, neutrophils
Pubmed
Web of science
Création de la notice
22/03/2021 19:41
Dernière modification de la notice
18/07/2024 7:06
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