NLRP1-dependent activation of Gasdermin D in neutrophils controls cutaneous leishmaniasis.

Details

Serval ID
serval:BIB_7C4D97BB2E62
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
NLRP1-dependent activation of Gasdermin D in neutrophils controls cutaneous leishmaniasis.
Journal
PLoS pathogens
Author(s)
Goris M., Passelli K., Peyvandi S., Díaz-Varela M., Billion O., Prat-Luri B., Demarco B., Desponds C., Termote M., Iniguez E., Dey S., Malissen B., Kamhawi S., Hurrell B.P., Broz P., Tacchini-Cottier F.
ISSN
1553-7374 (Electronic)
ISSN-L
1553-7366
Publication state
Published
Issued date
09/2024
Peer-reviewed
Oui
Volume
20
Number
9
Pages
e1012527
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
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.
Keywords
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
Yes
Create date
13/09/2024 15:06
Last modification date
24/09/2024 6:19
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