Regulated Arginine Metabolism in Immunopathogenesis of a Wide Range of Diseases: Is There a Way to Pass between Scylla and Charybdis?

Старикова, Е. А.; Rubinstein, Artem A.; Mammedova, Jennet T.; Isakov, Dmitry V.; Kudryavtsev, I. V.

doi:10.3390/cimb45040231

Cited by 9 publications

(4 citation statements)

References 241 publications

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“…One of the most evolutionarily ancient strategies used by microbes to interfere with immune response and immune evasion is based on nutrient depletion in the microenvironment of host cells [21,50]. Here, we investigated an effect of bacterial arginine-hydrolyzing enzyme, ADI, on human peripheral blood T cell activation and differentiation.…”

Section: Discussionmentioning

confidence: 99%

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Streptococcal Arginine Deiminase Inhibits T Lymphocyte Differentiation In Vitro

Starikova,

Mammedova,

Ozhiganova

et al. 2023

Microorganisms

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Pathogenic microbes use arginine-metabolizing enzymes as an immune evasion strategy. In this study, the impact of streptococcal arginine deiminase (ADI) on the human peripheral blood T lymphocytes function in vitro was studied. The comparison of the effects of parental strain (Streptococcus pyogenes M49-16) with wild type of ArcA gene and its isogenic mutant with inactivated ArcA gene (Streptococcus pyogenes M49-16delArcA) was carried out. It was found that ADI in parental strain SDSC composition resulted in a fivefold decrease in the arginine concentration in human peripheral blood mononuclear cell (PBMC) supernatants. Only parental strain SDSCs suppressed anti-CD2/CD3/CD28-bead-stimulated mitochondrial dehydrogenase activity and caused a twofold decrease in IL-2 production in PBMC. Flow cytometry analysis revealed that ADI decreased the percentage of CM (central memory) and increased the proportion of TEMRA (terminally differentiated effector memory) of CD4+ and CD8+ T cells subsets. Enzyme activity inhibited the proliferation of all CD8+ T cell subsets as well as CM, EM (effector memory), and TEMRA CD4+ T cells. One of the prominent ADI effects was the inhibition of autophagy processes in CD8+ CM and EM as well as CD4+ CM, EM, and TEMRA T cell subsets. The data obtained confirm arginine’s crucial role in controlling immune reactions and suggest that streptococcal ADI may downregulate adaptive immunity and immunological memory.

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Section: Discussionmentioning

confidence: 99%

“…Theoretically, even such a local arginine decrease can be sufficient to suppress immune cell functions. Pathogenic microbes expressing ADI may create metabolic background, resulting in alteration of immune reaction, nonproductive inflammation, and elevated risk of reinfection [21].…”

Section: Introductionmentioning

confidence: 99%

Streptococcal Arginine Deiminase Inhibits T Lymphocyte Differentiation In Vitro

Starikova,

Mammedova,

Ozhiganova

et al. 2023

Microorganisms

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“…Since the first case of pneumonia of unknown cause was reported in December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread rapidly worldwide, posing a significant threat to human health. Severe COVID-19 might also be accompanied by various complications, such as pneumonia, acute respiratory distress syndrome, and sepsis [15], which might be related to the immune dysfunction and cytokine storm caused by COVID-19 [16,17]. Simultaneously, many studies reported that many patients infected with the SARS-CoV-2 also have gastrointestinal symptoms, which include anorexia, nausea, vomiting, diarrhea, and abdominal pain.…”

Section: Introductionmentioning

confidence: 99%

Exploring Key Biomarkers and Common Pathogenesis of Seven Digestive System Cancers and Their Correlation with COVID-19

Xiong

Yang

et al. 2023

CIMB

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Digestive system cancer and COVID-19 significantly affect the digestive system, but the mechanism of interaction between COVID-19 and the digestive system cancers has not been fully elucidated. We downloaded the gene expression of COVID-19 and seven digestive system cancers (oral, esophageal, gastric, colorectal, hepatocellular, bile duct, pancreatic) from GEO and identified hub differentially expressed genes. Multiple verifications, diagnostic efficacy, prognostic analysis, functional enrichment and related transcription factors of hub genes were explored. We identified 23 common DEGs for subsequent analysis. CytoHubba identified nine hub genes (CCNA2, CCNB1, CDKN3, ECT2, KIF14, KIF20A, KIF4A, NEK2, TTK). TCGA and GEO data validated the expression and excellent diagnostic and prognostic ability of hub genes. Functional analysis revealed that the processes of cell division and the cell cycle were essential in COVID-19 and digestive system cancers. Furthermore, six related transcription factors (E2F1, E2F3, E2F4, MYC, TP53, YBX1) were involved in hub gene regulation. Via in vitro experiments, CCNA2, CCNB1, and MYC expression was verified in 25 colorectal cancer tissue pairs. Our study revealed the key biomarks and common pathogenesis of digestive system cancers and COVID-19. These may provide new ideas for further mechanistic research.

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“…Understanding the L-Arg metabolic pathways in specific pathological conditions is essential to treating the pathology. Therefore, discovering a therapy that regulates the metabolism of L-Arg remains difficult [17].…”

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confidence: 99%