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

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...

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Main Authors: E. A. Starikova, I. V. Kudryavtsev, L. A. Burova, A. M. Lebedeva, J. T. Mammedova, I. S. Freidlin
Format: Article
Language:Russian
Published: St. Petersburg branch of the Russian Association of Allergologists and Clinical Immunologists 2021-01-01
Series:Медицинская иммунология
Subjects:
Online Access:https://www.mimmun.ru/mimmun/article/view/2075
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author E. A. Starikova
I. V. Kudryavtsev
L. A. Burova
A. M. Lebedeva
J. T. Mammedova
I. S. Freidlin
author_facet E. A. Starikova
I. V. Kudryavtsev
L. A. Burova
A. M. Lebedeva
J. T. Mammedova
I. S. Freidlin
author_sort E. A. Starikova
collection DOAJ
description 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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spelling doaj.art-63d84360ae694e769c0082a9dd18e1572024-04-22T13:07:46ZrusSt. Petersburg branch of the Russian Association of Allergologists and Clinical ImmunologistsМедицинская иммунология1563-06252313-741X2021-01-012261121113010.15789/1563-0625-IOS-20751348Influence of streptococcal arginine deiminase on the leukocyte infiltration in murine air pouch modelE. A. Starikova0I. V. Kudryavtsev1L. A. Burova2A. M. Lebedeva3J. T. Mammedova4I. S. Freidlin5Institute of Experimental MedicineInstitute of Experimental MedicineInstitute of Experimental MedicineInstitute of Experimental MedicineInstitute of Experimental MedicineInstitute of Experimental MedicineNumerous 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.https://www.mimmun.ru/mimmun/article/view/2075arginine deiminases. pyogenesl-arginineinflammationleukocyte subpopulations
spellingShingle E. A. Starikova
I. V. Kudryavtsev
L. A. Burova
A. M. Lebedeva
J. T. Mammedova
I. S. Freidlin
Influence of streptococcal arginine deiminase on the leukocyte infiltration in murine air pouch model
Медицинская иммунология
arginine deiminase
s. pyogenes
l-arginine
inflammation
leukocyte subpopulations
title Influence of streptococcal arginine deiminase on the leukocyte infiltration in murine air pouch model
title_full Influence of streptococcal arginine deiminase on the leukocyte infiltration in murine air pouch model
title_fullStr Influence of streptococcal arginine deiminase on the leukocyte infiltration in murine air pouch model
title_full_unstemmed Influence of streptococcal arginine deiminase on the leukocyte infiltration in murine air pouch model
title_short Influence of streptococcal arginine deiminase on the leukocyte infiltration in murine air pouch model
title_sort influence of streptococcal arginine deiminase on the leukocyte infiltration in murine air pouch model
topic arginine deiminase
s. pyogenes
l-arginine
inflammation
leukocyte subpopulations
url https://www.mimmun.ru/mimmun/article/view/2075
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