Metabolic regulators of enigmatic inflammasomes in autoimmune diseases and crosstalk with innate immune receptors

Immunology. 2021 Aug;163(4):348-362. doi: 10.1111/imm.13326. Epub 2021 May 2.

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.

Keywords: GPCR signalling; complement system; gut microbiota; immunometabolic diseases; inflammasome; metabolic reprogramming.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Autoimmune Diseases / immunology
  • Autoimmune Diseases / metabolism*
  • Complement System Proteins / metabolism*
  • Gastrointestinal Microbiome
  • Humans
  • Immunity, Innate
  • Inflammasomes / metabolism*
  • Receptor Cross-Talk
  • Receptors, G-Protein-Coupled / metabolism*
  • Signal Transduction

Substances

  • Inflammasomes
  • Receptors, G-Protein-Coupled
  • Complement System Proteins