Role of arginine deiminase in thymic atrophy during experimental Streptococcus pyogenes infection

Старикова, Е. А.; Golovin, Alexander; Vasilyev, Kirill; Karaseva, Alena; Серебрякова, М. К.; Sokolov, A. V.; Kudryavtsev, I. V.; Bürova, Larissa A.; Voynova, Irina V.; Suvorov, Alexander; Vasilyev, V. B.; Freidlin, I. S.

doi:10.1111/sji.12734

Cited by 11 publications

(12 citation statements)

References 57 publications

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“…Opposite, arginine depletion could be manifested later, when the bacterial load and AD output in the site of pathogen invasion dramatically increase. In our previous research, using murine model of streptococcal infection we found a gradual arginine decrease in blood showing the lowest values on the fifth day of postinfection [26].…”

Section: Discussionmentioning

confidence: 76%

“…The study was carried out with S. pyogenes M49-16 isogenic mutant lacking the ability to make AD that has been constructed and characterized earlier [27]. An assay SDSCs prepared from the parental and mutant strains showed that significant AD activity was present in parental SDSC but none could be detected in mutant one [26]. It was established that parental and mutant strains SDSC did not exhibit toxic impact on human PBMCs (Tabl.…”

Section: Discussionmentioning

confidence: 99%

“…Obtaining supernatant of ultrasonic destroyed streptococci. S. pyogenes M49-16 delArcA strain was obtained and characterized as described earlier [26]. Supernatant of Destroyed Streptococcal Cells (SDSCs), containing biologically active intracellular components, were extracted from the cultures of parental S. pyogenes M49-16 and its isogenic mutant with arcA (AD) gene deletion S. pyogenes M49-16 delArcA.…”

Section: Methodsmentioning

confidence: 99%

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S. pyogenes M49-16 arginine deiminase inhibits proliferative activity of human peripheral blood lymphocytes

Starickova

Leveshko

Churakina

et al. 2020

Russian Journal of Infection and Immunity

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Arginine deiminase is one of three enzymes constituting the arginine deiminase system in bacteria. It was demonstrated that arginine deiminase exerts anti-proliferative effects on some primary and immortalized mouse and human cells. It is assumed that the inhibitory effect of arginine deiminase on cell proliferation might be related to its ability to result in the arginine exhaustion. T lymphocytes depend on arginine for proliferation, T-cell receptor complex expression, and the differentiation of memory cells. The aim of the current study was to investigate an impact streptococcal arginine deiminase on functions of human peripheral blood lymphocytes. For this, we comparatively analyzed effects of Supernatant of Destroyed Streptococcal Cells (SDSCs) derived from parental strain S. pyogenes M49-16 and its isogenic mutant S. pyogenes M49-16delArcA bearing inactivated arginine deiminase gene (ArcA) on immune cell functions.An impact of supernatants on cell viability was estimated by staining with DAPI dye. Cell proliferation was assessed by MTT-test and flow cytometry by using the method based on intracellular protein staining with vital fluorescent CFSE (carboxyfluoresceinsuccinimidylester) dye. In addition, the level of lymphocyte tyrosine phosphatase CD45 expression in various culturing conditions was evaluated. It was demonstrated that S. pyogenes M49-16 SDSCs had no impact on cells viability. Parental strain-derived SDSC exerted virtually no effect on intact cells proliferation, but considerably suppressed ConA-induced cell proliferation.At the same time, mutant strain-derived SDSC significantly stimulated spontaneous cell proliferation, but not that one after mitogen exposure. It was observed that increased proliferation was accompanied by upregulated CD45 expression, although it was not significant in all cases. These data allow to conclude that bacterial arginine deiminase could be one of pathogenicity factors able to limit lymphocyte proliferation and immune response and could be a part of pathogen strategy to suppress immune response in order to improve bacterial growth and dissemination.

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Section: Discussionmentioning

confidence: 76%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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S. pyogenes M49-16 arginine deiminase inhibits proliferative activity of human peripheral blood lymphocytes

Starickova

Leveshko

Churakina

et al. 2020

Russian Journal of Infection and Immunity

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“…Studies have shown that L-arginine is an important regulator of the mTOR signaling pathway (124), which is essential for the development of T cells (125). Based on this theory, a Russian team found that Streptococcus pyogenes infection could induce thymic atrophy in mice and confirmed that this atrophy was inextricably associated with the reduction of L-arginine in the bloodstream by arginine deiminase produced by Streptococcus pyogenes (75). In fact, many pathogens that cause thymic atrophy can express products that reduce L-arginine in the blood (126).…”

Section: Streptococcusmentioning

confidence: 99%

Infection-Associated Thymic Atrophy

Ming-li

Qian

et al. 2021

Front. Immunol.

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The thymus is a vital organ of the immune system that plays an essential role in thymocyte development and maturation. Thymic atrophy occurs with age (physiological thymic atrophy) or as a result of viral, bacterial, parasitic or fungal infection (pathological thymic atrophy). Thymic atrophy directly results in loss of thymocytes and/or destruction of the thymic architecture, and indirectly leads to a decrease in naïve T cells and limited T cell receptor diversity. Thus, it is important to recognize the causes and mechanisms that induce thymic atrophy. In this review, we highlight current progress in infection-associated pathogenic thymic atrophy and discuss its possible mechanisms. In addition, we discuss whether extracellular vesicles/exosomes could be potential carriers of pathogenic substances to the thymus, and potential drugs for the treatment of thymic atrophy. Having acknowledged that most current research is limited to serological aspects, we look forward to the possibility of extending future work regarding the impact of neural modulation on thymic atrophy.

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“…Истощение L-аргинина может являться одним из элементов стратегии патогена, направленной на ограничение или дисрегуляцию иммунных реакций, поэтому АД может рассматриваться как фактор патогенности, способствующий выживанию и персистированию патогена. Ранее в наших исследованиях была показана зависимость активности диссеминации S. pyogenes от их способности продуцировать АД [47]. Влияние АД на развитие воспаления в ходе инфекционного процесса до сих пор слабо изучено.…”

Section: Introductionunclassified

Influence of streptococcal arginine deiminase on the leukocyte infiltration in murine air pouch model

et al. 2021

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Numerous pathogens express arginine deiminase, an enzyme that catalyzes the hydrolysis of L-arginine in a chain of biochemical reactions aimed at the synthesis of ATP in bacterial cells. L-arginine is a semi-essential, proteinogenic amino acid that plays an important role in regulating the functions of the immune system cells in mammals. Depletion of L-arginine may cause a weakening of the immune reaction. In order to improve the conditions of dissemination, many pathogens use a strategy of L-arginine depletion in the microenvironment of host cells. Bacterial arginine deiminase can be a pathogenicity factor aimed for dysregulating the processes of inflammation and immune response. In general, the effect of arginine deiminase on immune cells may result into disturbed production of regulatory proinflammatory molecules, such as NO, and related substances, inhibition of activation, migration and differentiation of individual leukocyte subsets. The aim of this study was to investigate the effect of arginine deiminase on the formation of inflammatory infiltrate in murine air pouch model of streptococcal infection. Materials and methods: The study was performed using S. pyogenes M49-16 expressing arginine deiminase and its isogenic mutant S. pyogenes M49-16delArcA with inactivated arginine deiminase gene. The flow cytometry analysis of the inflammatory infiltrate leukocytes subpopulation in mice infected with the original strain of S. pyogenes M49-16 and its isogenic mutant S. pyogenes M49-16delArcA at different periods of infection was performed. It was shown that the inflammation reached its peak 6 hours after streptococcal inoculation, being more pronounced in mice infected with the mutant strain. Тhis finding was affirmed by a simultaneous and more pronounced increase in the absolute numbers of all leukocyte subsets in the focus of inflammation in this group of mice when compared to mice infected with original bacterial strain. Despite the decrease in the absolute number of all leukocyte types in the inflammatory infiltrate in both groups of mice for 24 hours, this trend was more pronounced in the group of mice infected with mutant microbial strain. Comparison of the inflammatory infiltrates developing in mice infected with original versus mutant strains showed that arginine deiminase may be a pathogenicity factor leading to dysregulation of protective immune response, due to impaired migration of white blood cells to the site of infection.

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Role of arginine deiminase in thymic atrophy during experimental Streptococcus pyogenes infection

Cited by 11 publications

References 57 publications

<i>S. pyogenes</i> M49-16 arginine deiminase inhibits proliferative activity of human peripheral blood lymphocytes

<i>S. pyogenes</i> M49-16 arginine deiminase inhibits proliferative activity of human peripheral blood lymphocytes

Infection-Associated Thymic Atrophy

Influence of streptococcal arginine deiminase on the leukocyte infiltration in murine air pouch model

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