ACOD1 in immunometabolism and disease - PubMed (original) (raw)

Review

ACOD1 in immunometabolism and disease

Runliu Wu et al. Cell Mol Immunol. 2020 Aug.

Abstract

Immunometabolism plays a fundamental role in health and diseases and involves multiple genes and signals. Aconitate decarboxylase 1 (ACOD1; also known as IRG1) is emerging as a regulator of immunometabolism in inflammation and infection. Upregulation of ACOD1 expression occurs in activated immune cells (e.g., macrophages and monocytes) in response to pathogen infection (e.g., bacteria and viruses), pathogen-associated molecular pattern molecules (e.g., LPS), cytokines (e.g., TNF and IFNs), and damage-associated molecular patterns (e.g., monosodium urate). Mechanistically, several immune receptors (e.g., TLRs and IFNAR), adapter proteins (e.g., MYD88), ubiquitin ligases (e.g., A20), and transcription factors (e.g., NF-κB, IRFs, and STATs) form complex signal transduction networks to control ACOD1 expression in a context-dependent manner. Functionally, ACOD1 mediates itaconate production, oxidative stress, and antigen processing and plays dual roles in immunity and diseases. On the one hand, activation of the ACOD1 pathway may limit pathogen infection and promote embryo implantation. On the other hand, abnormal ACOD1 expression can lead to tumor progression, neurodegenerative disease, and immune paralysis. Further understanding of the function and regulation of ACOD1 is important for the application of ACOD1-based therapeutic strategies in disease.

Keywords: ACOD1; disease; immunometabolism.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1

Fig. 1

Expression of ACOD1 in infection and immunity. a–c Many inflammatory stimuli (e.g., PAMPs, IFNs, TNF, and IL1B) can induce ACOD1 expression by activating receptors (e.g., TLRs, IFNAR, TNFR, and IL1R) and transcription factors (such as NF-κB, IRFs, and STATs) in a context-dependent manner

Fig. 2

Fig. 2

Function of ACOD1 in infection and immunity. a ACOD1-mediated itaconate production leads to NFE2L2 activation, SDH inhibition, isocitrate lyase inhibition, and prenylation induction. b ACOD1-mediated ROS production contributes to antigen processing, pathogen killing, and A20 modulation. c ACOD1 mediates the utilization of fatty acids in OXPHOS to produce mROS for bacterial killing

References

    1. Mogensen TH. Pathogen recognition and inflammatory signaling in innate immune defenses. Clin. Microbiol Rev. 2009;22:240–273. -PMC -PubMed
    1. Akira S, Uematsu S, Takeuchi O. Pathogen recognition and innate immunity. Cell. 2006;124:783–801. -PubMed
    1. Chaplin DD. Overview of the immune response. J. Allergy Clin. Immunol. 2010;125:S3–S23. -PMC -PubMed
    1. O’Neill LA, Kishton RJ, Rathmell J. A guide to immunometabolism for immunologists. Nat. Rev. Immunol. 2016;16:553–565. -PMC -PubMed
    1. Mathis D, Shoelson SE. Immunometabolism: an emerging frontier. Nat. Rev. Immunol. 2011;11:81. -PMC -PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources