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Irgm2 and Gate-16 cooperatively dampen targeting of caspase-11 to Gram-negative bacterial products
- Publication Year :
- 2020
- Publisher :
- Cold Spring Harbor Laboratory, 2020.
-
Abstract
- Inflammatory caspase-11 (rodent) and caspases-4 and -5 (human) detect gram-negative bacterial component LPS in the host cell cytosol, which promotes activation of the non-canonical inflammasome. Although non-canonical inflammasome-induced pyroptosis and IL-1 related cytokine release is of importance to mount an efficient immune response against various bacteria, its unrestrained activation drives sepsis. This suggests that cellular components might tightly control the threshold level of the non-canonical inflammasome in order to ensure efficient but not deleterious inflammatory response. Here we show that the IFN-inducible protein Irgm2 and the ATG8 family member Gate-16 cooperatively slow down non-canonical inflammasome activation both in macrophages and in vivo. Specifically, the Irgm2/Gate-16 axis dampens caspase-11 targeting to intracellular bacteria, which lower caspase-11-mediated pyroptosis and cytokine release. Specifically, deficiency in Irgm2 or Gate16 opens an alternative road for caspase-11 targeting to intracellular bacteria, independently of the classical pathway driven by the Guanylate Binding Proteins (GBPs). Thus, our findings provide new molecular effectors involved at fine-tuning the optimal non-canonical inflammasome response and add novel insights in the understanding of the immune pathways they control.
- Subjects :
- 0303 health sciences
Host cell cytosol
Chemistry
Intracellular parasite
medicine.medical_treatment
Pyroptosis
Inflammasome
Caspase-11
Cell biology
03 medical and health sciences
Classical complement pathway
0302 clinical medicine
Immune system
Cytokine
medicine
030217 neurology & neurosurgery
030304 developmental biology
medicine.drug
Subjects
Details
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....3406c23135a97b11c01e1c3e5f2c7195