Abstract

Nucleotide‐binding domain and leucine‐rich repeat receptor (NLR)‐mediated inflammasome activation is important in host response to microbes, danger‐associated molecular patterns (DAMPs) and metabolic disease. Some NLRs have been shown to interact with distinct cell metabolic pathways and cause negative regulation, tumorigenesis and autoimmune disorders, interacting with multiple innate immune receptors to modulate disease. NLR activation is therefore crucial in host response and in the regulation of metabolic pathways that can trigger a wide range of immunometabolic diseases or syndromes. However, the exact mode by which some of the less well‐studied NLR inflammasomes are activated, interact with other metabolites and immune receptors, and the role they play in the progression of metabolic diseases is still not fully elucidated. In this study, we review up‐to‐date evidence regarding NLR function in metabolic pathways and the interplay with other immune receptors involved in GPCR signalling, gut microbiota and the complement system, in order to gain a better understanding of its link to disease processes.

Highlights

  • Organisms have developed host defence mechanisms that protect from microbial pathogens

  • Increased antimicrobial peptide (AMP) leads to inhibition of inflammasome activation by activating the nutrient sensor AMP-­dependent protein kinase (AMPK), which causes a metabolic switch from glycolysis to Oxidative phosphorylation (OXPHOS), which is linked to anti-i­nflammatory, quiescent and contracting cell responses [10]

  • short-­chain fatty acid (SCFA) acetate binding to metabolite-­sensing receptors GPR43 and/ or GPCR109A has been shown to mediate a protective effect against colitis and drive activation of NLRP3 inflammasome in epithelial cells, showing caspase 1 activation and secretion of IL-1­8

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Summary

Introduction

Organisms have developed host defence mechanisms that protect from microbial pathogens. Activation of the NLRP3 inflammasome can be modulated by the metabolic state of a cell and acts as a general sensor of cellular homeostasis.

Results
Conclusion
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