Irgm2 and Gate-16 cooperatively dampen Gram-negative bacteria-induced caspase-11 response.
Caspase-11
Gate-16
Irgm2
infections/Interferons
non-canonical inflammasome
Journal
EMBO reports
ISSN: 1469-3178
Titre abrégé: EMBO Rep
Pays: England
ID NLM: 100963049
Informations de publication
Date de publication:
05 11 2020
05 11 2020
Historique:
received:
07
05
2020
revised:
11
09
2020
accepted:
25
09
2020
pubmed:
31
10
2020
medline:
28
4
2021
entrez:
30
10
2020
Statut:
ppublish
Résumé
Inflammatory caspase-11 (rodent) and caspases-4/5 (humans) detect the Gram-negative bacterial component LPS within the host cell cytosol, promoting activation of the non-canonical inflammasome. Although non-canonical inflammasome-induced pyroptosis and IL-1-related cytokine release are crucial to mount an efficient immune response against various bacteria, their unrestrained activation drives sepsis. This suggests that cellular components tightly control the threshold level of the non-canonical inflammasome in order to ensure efficient but non-deleterious inflammatory responses. Here, we show that the IFN-inducible protein Irgm2 and the ATG8 family member Gate-16 cooperatively counteract Gram-negative bacteria-induced non-canonical inflammasome activation, both in cultured macrophages and in vivo. Specifically, the Irgm2/Gate-16 axis dampens caspase-11 targeting to intracellular bacteria, which lowers caspase-11-mediated pyroptosis and cytokine release. Deficiency in Irgm2 or Gate16 induces both guanylate binding protein (GBP)-dependent and GBP-independent routes for caspase-11 targeting to intracellular bacteria. Our findings identify molecular effectors that fine-tune bacteria-activated non-canonical inflammasome responses and shed light on the understanding of the immune pathways they control.
Identifiants
pubmed: 33124769
doi: 10.15252/embr.202050829
pmc: PMC7645206
doi:
Substances chimiques
Autophagy-Related Protein 8 Family
0
GABARAPL2 protein, human
0
Inflammasomes
0
Lipopolysaccharides
0
Caspases
EC 3.4.22.-
Caspases, Initiator
EC 3.4.22.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e50829Subventions
Organisme : European Society of Clinical Microbiology and Infectious Diseases (ESCMID)
Organisme : EC | H2020 | H2020 Priority Excellent Science | H2020 European Research Council (ERC)
ID : INFLAME 804249
Organisme : Fondation pour la Recherche Médicale (FRM)
ID : AJE20151034460
Organisme : ATIP-Avenir
Organisme : Research ProGram on Emerging and Re-emerging Infectious Diseases
ID : JP19fk0108047
Organisme : Japanese Initiative for Progress of Research on Infectious Diseases for Global Epidemic
ID : JP19fm0208018
Organisme : MEXT | JST | Strategic International Collaborative Research Program (SICORP)
ID : 19jm0210067h
Organisme : Grant-in-Aid for Scientific Research on Innovative Areas
ID : 19H04809
Organisme : Grant-in-Aid for Scientific Research
ID : 18KK0226
Organisme : Grant-in-Aid for Scientific Research
ID : 18H02642
Organisme : Ministry of Education, Culture, Sports, Science and Technology of Japan
ID : 19H00970
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2020 The Authors.
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