ACOD1 in immunometabolism and disease

Wu, Runliu; Chen, Feng; Wang, Nian; Tang, Daolin; Kang, Rui

doi:10.1038/s41423-020-0489-5

Cited by 116 publications

(87 citation statements)

References 99 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Responses are similar by scale, or even stronger, than those caused by viruses. Unlike VRG, a suite of genes with the highest ranks either have unknown roles ( saxitoxin and tetrodotoxin-binding protein and catechol o-methyltransferase domain – number one and three in the list) or have not been reported in association with salmon diseases, for example, cell adhesion molecule ceacam20 ( 37 ) and regulator of immune metabolism irg1 ( aconitate decarboxylase) ( 38 ). Both enrichment analysis and the gene composition of BACT indicate high complexity and diversity of responses to bacteria.…”

Section: Resultsmentioning

confidence: 99%

Transcriptome Responses of Atlantic Salmon (Salmo salar L.) to Viral and Bacterial Pathogens, Inflammation, and Stress

et al. 2021

View full text Add to dashboard Cite

Transcriptomics provides valuable data for functional annotations of genes, the discovery of biomarkers, and quantitative assessment of responses to challenges. Meta-analysis of Nofima’s Atlantic salmon microarray database was performed for the selection of genes that have shown strong and reproducible expression changes. Using data from 127 experiments including 6440 microarrays, four transcription modules (TM) were identified with a total of 902 annotated genes: 161 virus responsive genes – VRG (activated with five viruses and poly I:C), genes that responded to three pathogenic bacteria (523 up and 33 down-regulated genes), inflammation not caused by infections – wounds, melanized foci in skeletal muscle and exposure to PAMP (180 up and 72 down-regulated genes), and stress by exercise, crowding and cortisol implants (33 genes). To assist the selection of gene markers, genes in each TM were ranked according to the scale of expression changes. In terms of functional annotations, association with diseases and stress was unknown or not reflected in public databases for a large part of genes, including several genes with the highest ranks. A set of multifunctional genes was discovered. Cholesterol 25-hydroxylase was present in all TM and 22 genes, including most differentially expressed matrix metalloproteinases 9 and 13 were assigned to three TMs. The meta-analysis has improved understanding of the defense strategies in Atlantic salmon. VRG have demonstrated equal or similar responses to RNA (SAV, IPNV, PRV, and ISAV), and DNA (gill pox) viruses, injection of bacterial DNA (plasmid) and exposure of cells to PAMP (CpG and gardiquimod) and relatively low sensitivity to inflammation and bacteria. Genes of the highest rank show preferential expression in erythrocytes. This group includes multigene families (gig and several trim families) and many paralogs. Of pathogen recognition receptors, only RNA helicases have shown strong expression changes. Most VRG (82%) are effectors with a preponderance of ubiquitin-related genes, GTPases, and genes of nucleotide metabolism. Many VRG have unknown roles. The identification of TMs makes possible quantification of responses and assessment of their interactions. Based on this, we are able to separate pathogen-specific responses from general inflammation and stress.

show abstract

Section: Resultsmentioning

confidence: 99%

Transcriptome Responses of Atlantic Salmon (Salmo salar L.) to Viral and Bacterial Pathogens, Inflammation, and Stress

et al. 2021

View full text Add to dashboard Cite

show abstract

“…FABP5 encodes a fatty acid binding-protein that promotes the activation of NF-kB signaling [ 51 ]. ACOD1 serves a multifaceted role in the innate immune response to pathogen infection (bacteria and viruses) and in cytokine signaling (TNF and interferons), and is associated with both Toll-like receptor and NF-kB signaling pathways [ 52 ]. Expression of TNFAIP2 is upregulated via the NF-kB pathway and mediates the inflammatory response [ 53 , 54 ].…”

Section: Discussionmentioning

confidence: 99%

Experimental Babesia rossi infection induces hemolytic, metabolic, and viral response pathways in the canine host

et al. 2021

View full text Add to dashboard Cite

Background Babesia rossi is a leading cause of morbidity and mortality among the canine population of sub-Saharan Africa, but pathogenesis remains poorly understood. Previous studies of B. rossi infection were derived from clinical cases, in which neither the onset of infection nor the infectious inoculum was known. Here, we performed controlled B. rossi inoculations in canines and evaluated disease progression through clinical tests and whole blood transcriptomic profiling. Results Two subjects were administered a low inoculum (104 parasites) while three received a high (108 parasites). Subjects were monitored for 8 consecutive days; anti-parasite treatment with diminazene aceturate was administered on day 4. Blood was drawn prior to inoculation as well as every experimental day for assessment of clinical parameters and transcriptomic profiles. The model recapitulated natural disease manifestations including anemia, acidosis, inflammation and behavioral changes. Rate of disease onset and clinical severity were proportional to the inoculum. To analyze the temporal dynamics of the transcriptomic host response, we sequenced mRNA extracted from whole blood drawn on days 0, 1, 3, 4, 6, and 8. Differential gene expression, hierarchical clustering, and pathway enrichment analyses identified genes and pathways involved in response to hemolysis, metabolic changes, and several arms of the immune response including innate immunity, adaptive immunity, and response to viral infection. Conclusions This work comprehensively characterizes the clinical and transcriptomic progression of B. rossi infection in canines, thus establishing a large mammalian model of severe hemoprotozoal disease to facilitate the study of host-parasite biology and in which to test novel anti-disease therapeutics. The knowledge gained from the study of B. rossi in canines will not only improve our understanding of this emerging infectious disease threat in domestic dogs, but also provide insight into the pathobiology of human diseases caused by Babesia and Plasmodium species.

show abstract

“…The decarboxylation is encoded by aconitate decarboxylase 1 (ACOD1), also named Irg1 (Michelucci et al, 2013 ). Irg1 overexpression leads to increased synthesis of endogenous itaconate (Wu et al, 2020 ). Catalytic conversion of isocitrate to α-ketoglutarate dehydrogenase further causes accumulation of citrate (itaconate precursor) (Nonnenmacher and Hiller, 2018 ).…”

Section: The Biosynthesis and Metabolism Of Itaconatementioning

confidence: 99%

The Emerging Application of Itaconate: Promising Molecular Targets and Therapeutic Opportunities

et al. 2021

View full text Add to dashboard Cite

Metabolites have recently been found to be involved in significant biological regulation and changes. Itaconate, an important intermediate metabolite isolated from the tricarboxylic acid cycle, is derived from cis-aconitate decarboxylation mediated by immune response gene 1 in mitochondrial matrix. Itaconate has emerged as a key autocrine regulatory component involved in the development and progression of inflammation and immunity. It could directly modify cysteine sites on functional substrate proteins which related to inflammasome, signal transduction, transcription, and cell death. Itaconate can be a connector among immunity, metabolism, and inflammation, which is of great significance for further understanding the mechanism of cellular immune metabolism. And it could be the potential choice for the treatment of inflammation and immune-related diseases. This study is a systematic review of the potential mechanisms of metabolite associated with different pathology conditions. We briefly summarize the structural characteristics and classical pathways of itaconate and its derivatives, with special emphasis on its promising role in future clinical application, in order to provide theoretical basis for future research and treatment intervention.

show abstract

ACOD1 in immunometabolism and disease

Cited by 116 publications

References 99 publications

Transcriptome Responses of Atlantic Salmon (Salmo salar L.) to Viral and Bacterial Pathogens, Inflammation, and Stress

Transcriptome Responses of Atlantic Salmon (Salmo salar L.) to Viral and Bacterial Pathogens, Inflammation, and Stress

Experimental Babesia rossi infection induces hemolytic, metabolic, and viral response pathways in the canine host

The Emerging Application of Itaconate: Promising Molecular Targets and Therapeutic Opportunities

Contact Info

Product

Resources

About