Streptococcal Arginine Deiminase Inhibits T Lymphocyte Differentiation In Vitro
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 (<i>Streptococcus...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-10-01
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| Series: | Microorganisms |
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| Online Access: | https://www.mdpi.com/2076-2607/11/10/2585 |
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| author | Eleonora A. Starikova Jennet T. Mammedova Arina Ozhiganova Tatiana A. Leveshko Aleksandra M. Lebedeva Alexey V. Sokolov Dmitry V. Isakov Alena B. Karaseva Larissa A. Burova Igor V. Kudryavtsev |
| author_facet | Eleonora A. Starikova Jennet T. Mammedova Arina Ozhiganova Tatiana A. Leveshko Aleksandra M. Lebedeva Alexey V. Sokolov Dmitry V. Isakov Alena B. Karaseva Larissa A. Burova Igor V. Kudryavtsev |
| author_sort | Eleonora A. Starikova |
| collection | DOAJ |
| description | 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 (<i>Streptococcus pyogenes</i> M49-16) with wild type of <i>ArcA</i> gene and its isogenic mutant with inactivated <i>ArcA</i> gene (<i>Streptococcus pyogenes</i> M49-16del<i>ArcA</i>) 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. |
| first_indexed | 2024-03-10T21:01:51Z |
| format | Article |
| id | doaj.art-a9a0047578de40b198b014d4ce3d5717 |
| institution | Directory Open Access Journal |
| issn | 2076-2607 |
| language | English |
| last_indexed | 2024-03-10T21:01:51Z |
| publishDate | 2023-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Microorganisms |
| spelling | doaj.art-a9a0047578de40b198b014d4ce3d57172023-11-19T17:29:00ZengMDPI AGMicroorganisms2076-26072023-10-011110258510.3390/microorganisms11102585Streptococcal Arginine Deiminase Inhibits T Lymphocyte Differentiation In VitroEleonora A. Starikova0Jennet T. Mammedova1Arina Ozhiganova2Tatiana A. Leveshko3Aleksandra M. Lebedeva4Alexey V. Sokolov5Dmitry V. Isakov6Alena B. Karaseva7Larissa A. Burova8Igor V. Kudryavtsev9Laboratory of Cellular Immunology, Department of Immunology, Institute of Experimental Medicine, 197022 St. Petersburg, RussiaLaboratory of General Immunology, Department of Immunology, Institute of Experimental Medicine, 197022 St. Petersburg, RussiaLaboratory of Cellular Immunology, Department of Immunology, Institute of Experimental Medicine, 197022 St. Petersburg, RussiaLaboratory of Cellular Immunology, Department of Immunology, Institute of Experimental Medicine, 197022 St. Petersburg, RussiaLaboratory of Cellular Immunology, Department of Immunology, Institute of Experimental Medicine, 197022 St. Petersburg, RussiaLaboratory of Biochemical Genetics, Department of Molecular Genetics, Institute of Experimental Medicine, 197022 St. Petersburg, RussiaMedical Faculty, First Saint Petersburg State I. Pavlov Medical University, 197022 St. Petersburg, RussiaLaboratory of Molecular Genetics of Pathogenic Microorganisms, Department of Molecular Microbiology, Institute of Experimental Medicine, 197022 St. Petersburg, RussiaLaboratory of Biomedical Microecology, Department of Molecular Microbiology, Institute of Experimental Medicine, 197022 St. Petersburg, RussiaLaboratory of Cellular Immunology, Department of Immunology, Institute of Experimental Medicine, 197022 St. Petersburg, RussiaPathogenic 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 (<i>Streptococcus pyogenes</i> M49-16) with wild type of <i>ArcA</i> gene and its isogenic mutant with inactivated <i>ArcA</i> gene (<i>Streptococcus pyogenes</i> M49-16del<i>ArcA</i>) 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.https://www.mdpi.com/2076-2607/11/10/2585memory T cellsproliferationdifferentiationautophagyarginine<i>Streptococcus pyogenes</i> |
| spellingShingle | Eleonora A. Starikova Jennet T. Mammedova Arina Ozhiganova Tatiana A. Leveshko Aleksandra M. Lebedeva Alexey V. Sokolov Dmitry V. Isakov Alena B. Karaseva Larissa A. Burova Igor V. Kudryavtsev Streptococcal Arginine Deiminase Inhibits T Lymphocyte Differentiation In Vitro Microorganisms memory T cells proliferation differentiation autophagy arginine <i>Streptococcus pyogenes</i> |
| title | Streptococcal Arginine Deiminase Inhibits T Lymphocyte Differentiation In Vitro |
| title_full | Streptococcal Arginine Deiminase Inhibits T Lymphocyte Differentiation In Vitro |
| title_fullStr | Streptococcal Arginine Deiminase Inhibits T Lymphocyte Differentiation In Vitro |
| title_full_unstemmed | Streptococcal Arginine Deiminase Inhibits T Lymphocyte Differentiation In Vitro |
| title_short | Streptococcal Arginine Deiminase Inhibits T Lymphocyte Differentiation In Vitro |
| title_sort | streptococcal arginine deiminase inhibits t lymphocyte differentiation in vitro |
| topic | memory T cells proliferation differentiation autophagy arginine <i>Streptococcus pyogenes</i> |
| url | https://www.mdpi.com/2076-2607/11/10/2585 |
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