Impact of intracellular innate immune receptors on immunometabolism

Wei-Chun Chou,Xin Li,Elena Rampanelli,Jenny P-Y Ting

doi:10.1038/s41423-021-00780-y

Abstract

Immunometabolism, which is the metabolic reprogramming of anaerobic glycolysis, oxidative phosphorylation, and metabolite synthesis upon immune cell activation, has gained importance as a regulator of the homeostasis, activation, proliferation, and differentiation of innate and adaptive immune cell subsets that function as key factors in immunity. Metabolic changes in epithelial and other stromal cells in response to different stimulatory signals are also crucial in infection, inflammation, cancer, autoimmune diseases, and metabolic disorders. The crosstalk between the PI3K–AKT–mTOR and LKB1–AMPK signaling pathways is critical for modulating both immune and nonimmune cell metabolism. The bidirectional interaction between immune cells and metabolism is a topic of intense study. Toll-like receptors (TLRs), cytokine receptors, and T and B cell receptors have been shown to activate multiple downstream metabolic pathways. However, how intracellular innate immune sensors/receptors intersect with metabolic pathways is less well understood. The goal of this review is to examine the link between immunometabolism and the functions of several intracellular innate immune sensors or receptors, such as nucleotide-binding and leucine-rich repeat-containing receptors (NLRs, or NOD-like receptors), absent in melanoma 2 (AIM2)-like receptors (ALRs), and the cyclic dinucleotide receptor stimulator of interferon genes (STING). We will focus on recent advances and describe the impact of these intracellular innate immune receptors on multiple metabolic pathways. Whenever appropriate, this review will provide a brief contextual connection to pathogenic infections, autoimmune diseases, cancers, metabolic disorders, and/or inflammatory bowel diseases.

Highlights

A growing number of studies have highlighted the intricate relationship between intracellular metabolism and inflammation
Extensive studies have shown the importance of metabolic reprogramming in both T and B cell receptor (TCR/BCR) signaling, as well as membrane-associated Toll-like receptors (TLRs), less is known about the role of intracellular innate immune receptors in immunometabolism
This suppressive effect depends on the ability of ethyl pyruvate (EP) to IL-1β [117]. These findings suggest that specific enzymes and attenuate mitochondrial damage and inhibit may function as immunoregula- DNA (mtDNA) release into the metabolic pathways differentially govern the assembly and activation of the NLRP3 inflammasome depending on the different lipids, such as coenzyme A-containing fatty acids and location and underlying pathology

Summary

Impact of intracellular innate immune receptors on immunometabolism

Immunometabolism, which is the metabolic reprogramming of anaerobic glycolysis, oxidative phosphorylation, and metabolite synthesis upon immune cell activation, has gained importance as a regulator of the homeostasis, activation, proliferation, and differentiation of innate and adaptive immune cell subsets that function as key factors in immunity. The crosstalk between the PI3K–AKT–mTOR and LKB1–AMPK signaling pathways is critical for modulating both immune and nonimmune cell metabolism. How intracellular innate immune sensors/receptors intersect with metabolic pathways is less well understood. The goal of this review is to examine the link between immunometabolism and the functions of several intracellular innate immune sensors or receptors, such as nucleotide-binding and leucine-rich repeat-containing receptors (NLRs, or NOD-like receptors), absent in melanoma 2 (AIM2)-like receptors (ALRs), and the cyclic dinucleotide receptor stimulator of interferon genes (STING). We will focus on recent advances and describe the impact of these intracellular innate immune receptors on multiple metabolic pathways. This review will provide a brief contextual connection to pathogenic infections, autoimmune diseases, cancers, metabolic disorders, and/or inflammatory bowel diseases

INTRODUCTION

ADDITIONAL INFORMATION