Hexokinase Is an Innate Immune Receptor for the Detection of Bacterial Peptidoglycan

Autor: David M. Underhill, Moshe Arditi, Hee Cheol Cho, Kenichi Shimada, Andrea J. Wolf, K. Mark Coggeshall, Courtney A. Becker, Narcis I. Popescu, Matthew L. Wheeler, Wenbin Liang, Christopher N. Reyes
Rok vydání: 2016
Předmět:
0301 basic medicine
Inflammasomes
Inbred C57BL
Medical and Health Sciences
Monocytes
chemistry.chemical_compound
Mice
Cell Wall
Immunologic
Models
NOD2
Hexokinase
Receptors
Receptors
Immunologic
Receptor
Pattern recognition receptor
Inflammasome
Acetylation
Biological Sciences
Mitochondria
Biochemistry
Glycolysis
Muramyl dipeptide
medicine.drug
Peptidoglycan
Biology
NLR Family
Models
Biological
General Biochemistry
Genetics and Molecular Biology
Article
Acetylglucosamine
03 medical and health sciences
NLR Family
Pyrin Domain-Containing 3 Protein
medicine
Animals
Humans
Inflammatory and immune system
Dendritic Cells
Biological
Pyrin Domain-Containing 3 Protein
Immunity
Innate
Mice
Inbred C57BL
Cytosol
030104 developmental biology
chemistry
Bacillus anthracis
Potassium
Energy Metabolism
Developmental Biology
Zdroj: Cell, vol 166, iss 3
Popis: Degradation of Gram-positive bacterial cell wall peptidoglycan in macrophage and dendritic cell phagosomes leads to activation of the NLRP3 inflammasome, a cytosolic complex that regulates processing and secretion of interleukin (IL)-1β and IL-18. While many inflammatory responses to peptidoglycan are mediated by detection of its muramyl dipeptide component in the cytosol by NOD2, we report here that NLRP3 inflammasome activation is caused by release of N-acetylglucosamine that is detected in the cytosol by the glycolytic enzyme hexokinase. Inhibition of hexokinase by N-acetylglucosamine causes its dissociation from mitochondria outer membranes, and we found that this is sufficient to activate the NLRP3 inflammasome. In addition, weobserved that glycolytic inhibitors and metabolicconditions affecting hexokinase function and localization induce inflammasome activation. While previous studies have demonstrated that signaling by pattern recognition receptors can regulate metabolic processes, this study shows that a metabolic enzyme can act as a pattern recognition receptor. PAPERCLIP.
Databáze: OpenAIRE
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