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Article

Streptococcal Arginine Deiminase Inhibits T Lymphocyte Differentiation In Vitro

by
Eleonora A. Starikova
1,2,*,
Jennet T. Mammedova
3,
Arina Ozhiganova
1,
Tatiana A. Leveshko
1,
Aleksandra M. Lebedeva
1,
Alexey V. Sokolov
4,
Dmitry V. Isakov
2,
Alena B. Karaseva
5,
Larissa A. Burova
6 and
Igor V. Kudryavtsev
1,2
1
Laboratory of Cellular Immunology, Department of Immunology, Institute of Experimental Medicine, 197022 St. Petersburg, Russia
2
Medical Faculty, First Saint Petersburg State I. Pavlov Medical University, 197022 St. Petersburg, Russia
3
Laboratory of General Immunology, Department of Immunology, Institute of Experimental Medicine, 197022 St. Petersburg, Russia
4
Laboratory of Biochemical Genetics, Department of Molecular Genetics, Institute of Experimental Medicine, 197022 St. Petersburg, Russia
5
Laboratory of Molecular Genetics of Pathogenic Microorganisms, Department of Molecular Microbiology, Institute of Experimental Medicine, 197022 St. Petersburg, Russia
6
Laboratory of Biomedical Microecology, Department of Molecular Microbiology, Institute of Experimental Medicine, 197022 St. Petersburg, Russia
*
Author to whom correspondence should be addressed.
Microorganisms 2023, 11(10), 2585; https://doi.org/10.3390/microorganisms11102585
Submission received: 5 September 2023 / Revised: 13 October 2023 / Accepted: 18 October 2023 / Published: 19 October 2023
(This article belongs to the Special Issue Group A Streptococcus: Infection, Immunity and Vaccine Development)
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Abstract

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.
Keywords: memory T cells; proliferation; differentiation; autophagy; arginine; Streptococcus pyogenes; arginine deiminase memory T cells; proliferation; differentiation; autophagy; arginine; Streptococcus pyogenes; arginine deiminase
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MDPI and ACS Style

Starikova, E.A.; Mammedova, J.T.; Ozhiganova, A.; Leveshko, T.A.; Lebedeva, A.M.; Sokolov, A.V.; Isakov, D.V.; Karaseva, A.B.; Burova, L.A.; Kudryavtsev, I.V. Streptococcal Arginine Deiminase Inhibits T Lymphocyte Differentiation In Vitro. Microorganisms 2023, 11, 2585. https://doi.org/10.3390/microorganisms11102585

AMA Style

Starikova EA, Mammedova JT, Ozhiganova A, Leveshko TA, Lebedeva AM, Sokolov AV, Isakov DV, Karaseva AB, Burova LA, Kudryavtsev IV. Streptococcal Arginine Deiminase Inhibits T Lymphocyte Differentiation In Vitro. Microorganisms. 2023; 11(10):2585. https://doi.org/10.3390/microorganisms11102585

Chicago/Turabian Style

Starikova, Eleonora A., Jennet T. Mammedova, Arina Ozhiganova, Tatiana A. Leveshko, Aleksandra M. Lebedeva, Alexey V. Sokolov, Dmitry V. Isakov, Alena B. Karaseva, Larissa A. Burova, and Igor V. Kudryavtsev. 2023. "Streptococcal Arginine Deiminase Inhibits T Lymphocyte Differentiation In Vitro" Microorganisms 11, no. 10: 2585. https://doi.org/10.3390/microorganisms11102585

APA Style

Starikova, E. A., Mammedova, J. T., Ozhiganova, A., Leveshko, T. A., Lebedeva, A. M., Sokolov, A. V., Isakov, D. V., Karaseva, A. B., Burova, L. A., & Kudryavtsev, I. V. (2023). Streptococcal Arginine Deiminase Inhibits T Lymphocyte Differentiation In Vitro. Microorganisms, 11(10), 2585. https://doi.org/10.3390/microorganisms11102585

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