Starikova Eleonora A, Mammedova Jennet T, Ozhiganova Arina, Leveshko Tatiana A, Lebedeva Aleksandra M, Sokolov Alexey V, Isakov Dmitry V, Karaseva Alena B, Burova Larissa A, Kudryavtsev Igor V
Laboratory of Cellular Immunology, Department of Immunology, Institute of Experimental Medicine, 197022 St. Petersburg, Russia.
Medical Faculty, First Saint Petersburg State I. Pavlov Medical University, 197022 St. Petersburg, Russia.
Microorganisms. 2023 Oct 19;11(10):2585. doi: 10.3390/microorganisms11102585.
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 ( M49-16) with wild type of gene and its isogenic mutant with inactivated gene ( M49-16del) 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.
致病性微生物利用精氨酸代谢酶作为一种免疫逃避策略。在本研究中，研究了链球菌精氨酸脱亚氨酶（ADI）对人外周血T淋巴细胞体外功能的影响。对携带野生型基因的亲本菌株（M49 - 16）及其基因失活的同基因突变体（M49 - 16del）的作用进行了比较。结果发现，亲本菌株SDSC成分中的ADI导致人外周血单个核细胞（PBMC）上清液中精氨酸浓度降低了五倍。只有亲本菌株SDSC抑制了抗CD2/CD3/CD28磁珠刺激的线粒体脱氢酶活性，并使PBMC中IL - 2的产生减少了两倍。流式细胞术分析显示，ADI降低了CD4 +和CD8 + T细胞亚群中CM（中央记忆）的百分比，并增加了TEMRA（终末分化效应记忆）的比例。酶活性抑制了所有CD8 + T细胞亚群以及CM、EM（效应记忆）和TEMRA CD4 + T细胞的增殖。ADI的一个显著作用是抑制CD8 + CM和EM以及CD4 + CM、EM和TEMRA T细胞亚群中的自噬过程。获得的数据证实了精氨酸在控制免疫反应中的关键作用，并表明链球菌ADI可能下调适应性免疫和免疫记忆。
