Research Progress on the Mechanism of Itaconate Regulating Macrophage Immunometabolism

Shi, Jia; Cai, Cheng

doi:10.3389/fimmu.2022.937247

Cited by 7 publications

(4 citation statements)

References 62 publications

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“…Since A. niger produces large amounts of citrate, which is the precursor of itaconate, the aim was to modify the natural citrate producer into an itaconate producer, with high potential for the production of resins, plastics, paints and fibers. Furthermore, itaconate, which is an immunomodulatory metabolite highly expressed in activated macrophages, has potential application in the treatment of inflammatory diseases [ 268 ]. The use of the P gas promoter led to a gradually increased production of itaconate, correlating with decreasing pH values [ 267 ].…”

Section: Recombinant Dna Strategiesmentioning

confidence: 99%

Strategies for the Development of Industrial Fungal Producing Strains

Salazar-Cerezo

Vries

Garrigues

2023

JoF

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The use of microorganisms in industry has enabled the (over)production of various compounds (e.g., primary and secondary metabolites, proteins and enzymes) that are relevant for the production of antibiotics, food, beverages, cosmetics, chemicals and biofuels, among others. Industrial strains are commonly obtained by conventional (non-GMO) strain improvement strategies and random screening and selection. However, recombinant DNA technology has made it possible to improve microbial strains by adding, deleting or modifying specific genes. Techniques such as genetic engineering and genome editing are contributing to the development of industrial production strains. Nevertheless, there is still significant room for further strain improvement. In this review, we will focus on classical and recent methods, tools and technologies used for the development of fungal production strains with the potential to be applied at an industrial scale. Additionally, the use of functional genomics, transcriptomics, proteomics and metabolomics together with the implementation of genetic manipulation techniques and expression tools will be discussed.

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Section: Recombinant Dna Strategiesmentioning

confidence: 99%

Strategies for the Development of Industrial Fungal Producing Strains

Salazar-Cerezo

Vries

Garrigues

2023

JoF

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“…Metabolites of the TCA cycle reprogram the metabolism and epigenetics of immune cells, enabling them to perform different functions [ 6 , 7 ]. Immune responsive gene 1 ( IRG1 ), which encodes cis-aconitate decarboxylase (CAD), a metabolic enzyme of TCA cycle, catalyzes the decarboxylation of cis-aconitate to produce itaconate [ 8 ]. Itaconate is highly expressed in activated macrophages, which can influence metabolite and mitochondrial respiration changes in macrophages [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

Metabolite itaconate in host immunoregulation and defense

Yang,

Wang,

Tao

et al. 2023

Cell Mol Biol Lett

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Metabolic states greatly influence functioning and differentiation of immune cells. Regulating the metabolism of immune cells can effectively modulate the host immune response. Itaconate, an intermediate metabolite derived from the tricarboxylic acid (TCA) cycle of immune cells, is produced through the decarboxylation of cis-aconitate by cis-aconitate decarboxylase in the mitochondria. The gene encoding cis-aconitate decarboxylase is known as immune response gene 1 (IRG1). In response to external proinflammatory stimulation, macrophages exhibit high IRG1 expression. IRG1/itaconate inhibits succinate dehydrogenase activity, thus influencing the metabolic status of macrophages. Therefore, itaconate serves as a link between macrophage metabolism, oxidative stress, and immune response, ultimately regulating macrophage function. Studies have demonstrated that itaconate acts on various signaling pathways, including Keap1-nuclear factor E2-related factor 2-ARE pathways, ATF3–IκBζ axis, and the stimulator of interferon genes (STING) pathway to exert antiinflammatory and antioxidant effects. Furthermore, several studies have reported that itaconate affects cancer occurrence and development through diverse signaling pathways. In this paper, we provide a comprehensive review of the role IRG1/itaconate and its derivatives in the regulation of macrophage metabolism and functions. By furthering our understanding of itaconate, we intend to shed light on its potential for treating inflammatory diseases and offer new insights in this field.

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“…Itaconate (ITA), a signaling metabolite produced by classically activated macrophages (7), regulates the immune, inflammatory, and oxidative responses to infection (8)(9)(10). The intrinsic pathway of endogenous ITA production in macrophages requires immuneresponsive gene 1 (IRG1), also known as aconitate decarboxylase 1 (ACOD1), to decarboxylate cis-aconitate (Figure 1) (11).…”

Section: Introductionmentioning

confidence: 99%

“…ITA, its esterified derivatives (4-OI and DMI), and its naturally occurring isomers (mesaconate and citraconate) make considerable contributions to infectious and inflammatory diseases. Indeed, the anti-infective and anti-inflammatory roles of ITA and its isomers and esterified derivatives have been discussed (8)(9)(10)(21)(22)(23). Here, we review the regulation of endogenous ITA production in terms of immunometabolic networks and the functions of ITA and its relatives during infection.…”

Section: Introductionmentioning

confidence: 99%

Itaconate family-based host-directed therapeutics for infections

et al. 2023

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Itaconate is a crucial anti-infective and anti-inflammatory immunometabolite that accumulates upon disruption of the Krebs cycle in effector macrophages undergoing inflammatory stress. Esterified derivatives of itaconate (4-octyl itaconate and dimethyl itaconate) and its isomers (mesaconate and citraconate) are promising candidate drugs for inflammation and infection. Several itaconate family members participate in host defense, immune and metabolic modulation, and amelioration of infection, although opposite effects have also been reported. However, the precise mechanisms by which itaconate and its family members exert its effects are not fully understood. In addition, contradictory results in different experimental settings and a lack of clinical data make it difficult to draw definitive conclusions about the therapeutic potential of itaconate. Here we review how the immune response gene 1-itaconate pathway is activated during infection and its role in host defense and pathogenesis in a context-dependent manner. Certain pathogens can use itaconate to establish infections. Finally, we briefly discuss the major mechanisms by which itaconate family members exert antimicrobial effects. To thoroughly comprehend how itaconate exerts its anti-inflammatory and antimicrobial effects, additional research on the actual mechanism of action is necessary. This review examines the current state of itaconate research in infection and identifies the key challenges and opportunities for future research in this field.

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Research Progress on the Mechanism of Itaconate Regulating Macrophage Immunometabolism

Cited by 7 publications

References 62 publications

Strategies for the Development of Industrial Fungal Producing Strains

Strategies for the Development of Industrial Fungal Producing Strains

Metabolite itaconate in host immunoregulation and defense

Itaconate family-based host-directed therapeutics for infections

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