Guanylate-binding protein 5 licenses caspase-11 for Gasdermin-D mediated host resistance to Brucella abortus infection.

Details

Ressource 1Download: journal.ppat.1007519.pdf (3020.18 [Ko])
State: Public
Version: Final published version
Serval ID
serval:BIB_657DFCFBDA80
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Guanylate-binding protein 5 licenses caspase-11 for Gasdermin-D mediated host resistance to Brucella abortus infection.
Journal
PLoS pathogens
Author(s)
Cerqueira D.M., Gomes MTR, Silva ALN, Rungue M., Assis NRG, Guimarães E.S., Morais S.B., Broz P., Zamboni D.S., Oliveira S.C.
ISSN
1553-7374 (Electronic)
ISSN-L
1553-7366
Publication state
Published
Issued date
12/2018
Peer-reviewed
Oui
Volume
14
Number
12
Pages
e1007519
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Abstract
Innate immune response against Brucella abortus involves activation of Toll-like receptors (TLRs) and NOD-like receptors (NLRs). Among the NLRs involved in the recognition of B. abortus are NLRP3 and AIM2. Here, we demonstrate that B. abortus triggers non-canonical inflammasome activation dependent on caspase-11 and gasdermin-D (GSDMD). Additionally, we identify that Brucella-LPS is the ligand for caspase-11 activation. Interestingly, we determine that B. abortus is able to trigger pyroptosis leading to pore formation and cell death, and this process is dependent on caspase-11 and GSDMD but independently of caspase-1 protease activity and NLRP3. Mice lacking either caspase-11 or GSDMD were significantly more susceptible to infection with B. abortus than caspase-1 knockout or wild-type animals. Additionally, guanylate-binding proteins (GBPs) present in mouse chromosome 3 participate in the recognition of LPS by caspase-11 contributing to non-canonical inflammasome activation as observed by the response of Gbpchr3-/- BMDMs to bacterial stimulation. We further determined by siRNA knockdown that among the GBPs contained in mouse chromosome 3, GBP5 is the most important for Brucella LPS to be recognized by caspase-11 triggering IL-1β secretion and LDH release. Additionally, we observed a reduction in neutrophil, dendritic cell and macrophage influx in spleens of Casp11-/- and Gsdmd-/- compared to wild-type mice, indicating that caspase-11 and GSDMD are implicated in the recruitment and activation of immune cells during Brucella infection. Finally, depletion of neutrophils renders wild-type mice more susceptible to Brucella infection. Taken together, these data suggest that caspase-11/GSDMD-dependent pyroptosis triggered by B. abortus is important to infection restriction in vivo and contributes to immune cell recruitment and activation.
Keywords
Animals, Apoptosis Regulatory Proteins/immunology, Brucella abortus, Brucellosis/immunology, Caspases/immunology, GTP-Binding Proteins/immunology, Immunity, Innate/immunology, Mice, Mice, Inbred C57BL, Mice, Knockout
Pubmed
Web of science
Open Access
Yes
Create date
17/01/2019 15:50
Last modification date
20/08/2019 15:21
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