Differentiation of immunomodulatory effects of arginyl-alpha-aspartyl-lysyl-valyl-tyrosyl-arginine and glucosaminylmuramyldipeptide on effector functions and phenotype of functionally significant subpopulations of neutrophilic granulocytes in an experimental model of viral-bacterial coinfection [Дифференцированность иммуномодулирующих эффектов аргинил-альфа-аспартил-лизил-валил-тирозил-аргинина и глюкозаминилмурамилдипептида на эффекторные функции и фенотип функционально значимых субпопуляций нейтрофильных гранулоцитов в экспериментальной модели вирусно-бактериальной коинфекции]

Introduction. The emergence of atypical infectious and inflammatory diseases, that are difficult to respond to standard therapy, is associated with the increasing frequency of manifestations of the combined pathology of coinfection and antibiotic resistance, which is a serious clinical problem. Clarification of the mechanisms of defective neutrophilic granulocytes (NG) functioning responsible for the emerging negative synergism of viruses and bacteria is urgent, and the assessment of the possibility of reorienting the functional potential of NG under the influence of immunotropic substances can allow creatingon of the new immunotherapeutic approaches for more effective treatment of viral-bacterial coinfections. Aim of the study in model of viral-bacterial co-infection in vitro to assess the effect of arginyl-alpha-aspartyl-lysyl-valyl-tyrosyl-arginine and glucosaminylmuramyldipeptide on the effector functions of neutrophilic granulocytes (NG) and the phenotype of functionally significant subpopulations CD64–CD32+CD16+CD11b+NG, CD64+CD32+CD16+CD11b+NG. Material and methods. A study of 56 samples of peripheral blood (PВ) of apparently healthy adults was carried out. By sequential incubation of PВ with dsRNA, fMLP the experimental model of viral-bacterial co-infection was reproduced. A comparative assessment of the effect of hexapeptide arginyl-alpha-aspartyl-lysyl-valyl-tyrosyl-arginine (НP) and glucosaminylmuramyldipeptide (GMDP) on the phenotype and content of functionally significant subpopulations CD64–CD32+CD16+CD11b+-NG, CD64+CD32+CD16+CD11b+-NG was carried out in the coinfections experimental model in an in vitro system; on activity NADPH oxidases of NG in NBT-test spontaneous and stimulated by Staphylococcus aureus (strain 209); on phagocytic function with S. aureus (strain 209): %FAN – % active phagocytic NG, % inactive NG (%ING), % NET – %NG formed NET, %NG in apoptosis. Results. It was found that HP additionally activated the phenotype of the subpopulation previously activated in the experimental model СD64–CD16midCD32brightCD11bbright-NG significantly reduced the number of NGs in the CD64+CD32+CD16+CD11b+-NG subpopulation, changing its phenotype to СD64brightCD16midCD32midCD11bmid-NG. GMDP did not affect the number of NGs in the CD64–CD32+CD16+CD11b+ subpopulation, however, it caused a decrease in the expression density of all membrane receptors СD64–CD16dimCD32dimCD11bdim-NG to the level of those in comparison group 1. In parallel, there was a decrease in the number of NGs in the activated subpopulation СD64+CD16+CD32+CD11b+-NGs, which was accompanied by a change in the phenotype in СD64midCD16dimCD32midCD11bmid-NGs. Conclusion. The revealed differentiated effects of HP and GMDP effects on the content and phenotype of functionally significant NG subpopulations transformed in the experimental model of viral-bacterial coinfection can serve as a basis for the development of various immunotherapeutic strategies aimed at restoration of the normal NG function depending on the depth of the identified disorders. © 2022 Meditsina Publishers. All rights reserved.

Nesterova I.V. 1, 2, 3 , Chudilova G.A. 1 , Chapurina V.N.1 , Kovaleva S.V. 1 , Lomtatidze L.V. 1 , Tarakanov V.A.1 , Teterin Yu.V.1 , Pirogova A.I.1
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  • 1 Kuban State Medical University of the Ministry of Health of the Russian Federation, Krasnodar, 350063, Russian Federation
  • 2 Peoples’ Friendship University of Russia of the Ministry of Science and Higher Education of the Russian Federation, Moscow, 117198, Russian Federation
  • 3 FCME of the Medical Institute, RUDN of the MSHE of Russia, Moscow, Russian Federation
Ключевые слова
arginyl-alpha-aspartyl-lysyl-valyl-tyrosyl-arginine; co-infection model; glucosaminylmuramyl dipeptide; neutrophilic granulocytes; phenotype; subpopulations
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