NLRP1-dependent activation of Gasdermin D in neutrophils controls cutaneous leishmaniasis.
Détails
ID Serval
serval:BIB_7C4D97BB2E62
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
NLRP1-dependent activation of Gasdermin D in neutrophils controls cutaneous leishmaniasis.
Périodique
PLoS pathogens
ISSN
1553-7374 (Electronic)
ISSN-L
1553-7366
Statut éditorial
Publié
Date de publication
09/2024
Peer-reviewed
Oui
Volume
20
Numéro
9
Pages
e1012527
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: epublish
Publication Status: epublish
Résumé
Intracellular pathogens that replicate in host myeloid cells have devised ways to inhibit the cell's killing machinery. Pyroptosis is one of the host strategies used to reduce the pathogen replicating niche and thereby control its expansion. The intracellular Leishmania parasites can survive and use neutrophils as a silent entry niche, favoring subsequent parasite dissemination into the host. Here, we show that Leishmania mexicana induces NLRP1- and caspase-1-dependent Gasdermin D (GSDMD)-mediated pyroptosis in neutrophils, a process critical to control the parasite-induced pathology. In the absence of GSDMD, we observe an increased number of infected dermal neutrophils two days post-infection. Using adoptive neutrophil transfer in neutropenic mice, we show that pyroptosis contributes to the regulation of the neutrophil niche early after infection. The critical role of neutrophil pyroptosis and its positive influence on the regulation of the disease outcome was further demonstrated following infection of mice with neutrophil-specific deletion of GSDMD. Thus, our study establishes neutrophil pyroptosis as a critical regulator of leishmaniasis pathology.
Mots-clé
Animals, Neutrophils/metabolism, Neutrophils/immunology, Phosphate-Binding Proteins/metabolism, Mice, Leishmaniasis, Cutaneous/immunology, Leishmaniasis, Cutaneous/metabolism, Leishmaniasis, Cutaneous/parasitology, Pyroptosis, Intracellular Signaling Peptides and Proteins/metabolism, Intracellular Signaling Peptides and Proteins/genetics, Apoptosis Regulatory Proteins/metabolism, Mice, Inbred C57BL, Mice, Knockout, Adaptor Proteins, Signal Transducing/metabolism, Adaptor Proteins, Signal Transducing/genetics, Leishmania mexicana/immunology, Gasdermins
Pubmed
Web of science
Open Access
Oui
Création de la notice
13/09/2024 15:06
Dernière modification de la notice
24/09/2024 6:19