Pub Date : 2024-07-28DOI: 10.15789/2220-7619-lnr-16889
M. Gulimov, N. O. Kalyuzhnaya, Yulia I. Ammour, V. Zverev, O. A. Svitich
Introduction. Rubella virus is an RNA-containing virus capable of infecting human cells and causing infectious disease. Infection of pregnant women with rubella virus can lead to abortion or congenital rubella syndrome (CRS), a set of long-term birth defects including incomplete fetal organ development and mental retardation. There is no specific treatment for rubella and CRS. The regulation of antiviral immune response and viral reproduction by long non-coding RNAs is currently under active investigation. In this study, we evaluated the changes in the expression profile of long non-coding RNAs in rubella virus-infected A549 epithelial by RNA sequencing. Materials and Methods. A549 cells were infected with a wild-type variant of laboratory strain C-77 of rubella virus with a multiplicity of infection of 1.0 infectious units per cell and incubated for 72 hours. Virus titres were determined by the CCID method in the sensitive RK-13 cell culture. 48 h after infection, the cell monolayer was lysed, RNA was isolated, and libraries were prepared for sequencing. Sequencing was performed on the NextSeq500 platform (Illumina, USA) in paired-end reading mode. Validation of the obtained RNA sequencing data was performed using quantitative real-time PCR. Results. Rubella virus replication affects the production of some long non-coding RNAs by altering their expression profile. Thus, upon infection of A549 epithelial cells with rubella virus, there was a significant increase in the expression of such long non-coding RNAs as GAS5, NEAT1, LUCAT1, MIR210HG, MEG3, EPB41L4A-AS1, ZFAS1, and SNHG 1, 7, 12, 29, 32. DANCR, IGFL2-AS1, IGFL2-AS1, MIR1915HG, and SNHG14 were most significantly decreased in expression. Gene ontology (GO)-analysis revealed that long non-coding RNAs are involved at different levels in the mechanisms of immune response, in particular, RNA processing and nucleic acid metabolism; therefore, up- and down-regulation of these molecules leads to modulation of human antiviral immune response in response to rubella virus infection. Conclusion. Thus, the regulation of long non-coding RNA production by rubella virus has been shown for the first time. Differentially expressed long non-coding RNAs can be used as prognostic and diagnostic biomarkers of viral diseases.
{"title":"Long non-coding RNAs — regulators of rubella virus infection and antiviral response","authors":"M. Gulimov, N. O. Kalyuzhnaya, Yulia I. Ammour, V. Zverev, O. A. Svitich","doi":"10.15789/2220-7619-lnr-16889","DOIUrl":"https://doi.org/10.15789/2220-7619-lnr-16889","url":null,"abstract":"Introduction. Rubella virus is an RNA-containing virus capable of infecting human cells and causing infectious disease. Infection of pregnant women with rubella virus can lead to abortion or congenital rubella syndrome (CRS), a set of long-term birth defects including incomplete fetal organ development and mental retardation. There is no specific treatment for rubella and CRS. The regulation of antiviral immune response and viral reproduction by long non-coding RNAs is currently under active investigation. In this study, we evaluated the changes in the expression profile of long non-coding RNAs in rubella virus-infected A549 epithelial by RNA sequencing. Materials and Methods. A549 cells were infected with a wild-type variant of laboratory strain C-77 of rubella virus with a multiplicity of infection of 1.0 infectious units per cell and incubated for 72 hours. Virus titres were determined by the CCID method in the sensitive RK-13 cell culture. 48 h after infection, the cell monolayer was lysed, RNA was isolated, and libraries were prepared for sequencing. Sequencing was performed on the NextSeq500 platform (Illumina, USA) in paired-end reading mode. Validation of the obtained RNA sequencing data was performed using quantitative real-time PCR. Results. Rubella virus replication affects the production of some long non-coding RNAs by altering their expression profile. Thus, upon infection of A549 epithelial cells with rubella virus, there was a significant increase in the expression of such long non-coding RNAs as GAS5, NEAT1, LUCAT1, MIR210HG, MEG3, EPB41L4A-AS1, ZFAS1, and SNHG 1, 7, 12, 29, 32. DANCR, IGFL2-AS1, IGFL2-AS1, MIR1915HG, and SNHG14 were most significantly decreased in expression. Gene ontology (GO)-analysis revealed that long non-coding RNAs are involved at different levels in the mechanisms of immune response, in particular, RNA processing and nucleic acid metabolism; therefore, up- and down-regulation of these molecules leads to modulation of human antiviral immune response in response to rubella virus infection. Conclusion. Thus, the regulation of long non-coding RNA production by rubella virus has been shown for the first time. Differentially expressed long non-coding RNAs can be used as prognostic and diagnostic biomarkers of viral diseases.","PeriodicalId":21412,"journal":{"name":"Russian Journal of Infection and Immunity","volume":"2 11","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141797127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-28DOI: 10.15789/2220-7619-pcs-16766
Olga V. Berdiugina
Introduction. Post-COVID syndrome (alternatively: chronic COVID syndrome, post-acute sequelae of COVID-19, long-haul COVID, long COVID, PASC, CCS) is a state of permanent or permanent presence of symptoms of a pathological process after COVID-19. Currently, there is no consensus on the timing of the onset of post-COVID-19 syndrome. The purpose of this study was to analyze the appearance of some post-COVID symptoms 1, 2 and 3 months after infection with the SARS-CoV-2 virus. Materials and methods. The analysis of clinical and laboratory data of 59 medical workers who had a mild or moderate form of COVID-19 was carried out. Three groups were formed: with the assessment of post-COVID-19 changes 1 month after the onset of the disease; with the detection of changes after 2 months; and with the detection of dysfunctions after 3 months. Results and discussion. It was found that 57.7% of respondents complained of fatigue, weakness, sleep disorders in the first month of observation. After 2 months, the frequency of complaints decreased by 42.3%, and by 3 months it increased again by 15.6%. A month after COVID-19, several cases were recorded when employees were unable to perform any, even very light, work. However, by 3 months of follow-up, 96.2% of the surveyed declared full recovery of efficiency. The appearance of muscle, joint, and spinal pain was reported more often in the first month after COVID-19, then the number of complaints decreased by half to 23–25% of the total number of observations. The assessment of the severity of the infection among the respondents of the three groups did not reveal significant differences between the data in 1, 2 and 3 months after COVID-19. Conclusion. An analysis of some post-COVID symptoms showed that in mild and moderate COVID-19, manifestations are observed 1, 2 and 3 months after infection with the SARS-CoV-2 virus. Multidirectional change dynamics were revealed, more often accompanied by a decrease in the manifestation of post-COVID syndrome 2 months after coronavirus infection, which may create a false impression of an absence of signs of post-COVID syndrome during this period.
{"title":"Post-COVID-19 syndrome: a discussion of onset timing","authors":"Olga V. Berdiugina","doi":"10.15789/2220-7619-pcs-16766","DOIUrl":"https://doi.org/10.15789/2220-7619-pcs-16766","url":null,"abstract":"Introduction. Post-COVID syndrome (alternatively: chronic COVID syndrome, post-acute sequelae of COVID-19, long-haul COVID, long COVID, PASC, CCS) is a state of permanent or permanent presence of symptoms of a pathological process after COVID-19. Currently, there is no consensus on the timing of the onset of post-COVID-19 syndrome. The purpose of this study was to analyze the appearance of some post-COVID symptoms 1, 2 and 3 months after infection with the SARS-CoV-2 virus. Materials and methods. The analysis of clinical and laboratory data of 59 medical workers who had a mild or moderate form of COVID-19 was carried out. Three groups were formed: with the assessment of post-COVID-19 changes 1 month after the onset of the disease; with the detection of changes after 2 months; and with the detection of dysfunctions after 3 months. Results and discussion. It was found that 57.7% of respondents complained of fatigue, weakness, sleep disorders in the first month of observation. After 2 months, the frequency of complaints decreased by 42.3%, and by 3 months it increased again by 15.6%. A month after COVID-19, several cases were recorded when employees were unable to perform any, even very light, work. However, by 3 months of follow-up, 96.2% of the surveyed declared full recovery of efficiency. The appearance of muscle, joint, and spinal pain was reported more often in the first month after COVID-19, then the number of complaints decreased by half to 23–25% of the total number of observations. The assessment of the severity of the infection among the respondents of the three groups did not reveal significant differences between the data in 1, 2 and 3 months after COVID-19. Conclusion. An analysis of some post-COVID symptoms showed that in mild and moderate COVID-19, manifestations are observed 1, 2 and 3 months after infection with the SARS-CoV-2 virus. Multidirectional change dynamics were revealed, more often accompanied by a decrease in the manifestation of post-COVID syndrome 2 months after coronavirus infection, which may create a false impression of an absence of signs of post-COVID syndrome during this period.","PeriodicalId":21412,"journal":{"name":"Russian Journal of Infection and Immunity","volume":"8 11","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141797166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-28DOI: 10.15789/2220-7619-bca-16695
O. Radaeva, A. Simbirtsev, M. Iskandyarova, E. Negodnova, V. Kulyapkin, K. Krasnoglazova, V. V. Eremeev
The search for predictors of the severe course of COVID-19 was relevant both during the pandemic and at the present time. The aim of the study was to analyze the relationship of cytokine levels in patients with EН before SARS-CoV-2 infection with the incidence of coronavirus pneumonia. Materials and methods. From the database of 290 patients with stage II EAG who have been under observation for 8–12 years with annual blood sampling to determine cytokine levels, COVID-19 survivors were selected (mild without pneumonia and moderate to severe, pneumonia CT 1–2, CT-3). Anamnestic levels of IL-1β, IL-1α, IL-1ra, IL-18, IL-18 BP, IL-37, IL-6, sIL-6r, M-CSF, VEGF-A, IL-34 and HMGB1) in the blood serum of patients with stage II EH were analyzed (method ELISA). The analysis of the obtained results was carried out using Stat Soft Statistica 13.5. Results and discussion. Patients with EH and COVID-19 with pneumonia (CT I-II) after SARS-CoV-2 infection 2–6 months before the infectious disease had significantly higher serum levels: IL-1α (p 0.05) and a decrease in IL-37 (p 0.001). During multivariate correlation analysis, a statistically independent relationship between an increase in the incidence of viral pneumonia in patients with stage II EН was confirmed only for IL-37 with a blood level of less than 60.2 pg/ml (regression coefficient — 2.21, standard error — 0.28, t criterion — 6.12, relative risk — 2.52, criterion Walda — 7.92, p = 0.006). When studying circadian rhythms of cytokine content in blood serum in patients of the analyzed groups, calculating the strength of correlations of anamnestic evening IL-37 levels in patients with stage II EР at 19.00–20.00 with the frequency of pneumonia against the background of SARS-CoV-2 infection, it has greater specificity and sensitivity (specificity — 0.75, sensitivity — 0.82) than morning concentrations. Considering that data on circadian rhythms were obtained in a limited number of patients, further monitoring is necessary, which is carried out by our scientific group. It should be noted that patients with essential hypertension are pathogenetically heterogeneous, including in terms of cytokine regulation. The study of this area will make it possible to personalize cytokine phenotypes of the disease and develop new methods for calculating the prognosis of both cardiovascular complications and features of the course of infectious diseases.
{"title":"Blood cytokines as potential predictors of the development of SARS-CoV-2 associated pneumonia in patients with stage II ESSENTIAL hypertension","authors":"O. Radaeva, A. Simbirtsev, M. Iskandyarova, E. Negodnova, V. Kulyapkin, K. Krasnoglazova, V. V. Eremeev","doi":"10.15789/2220-7619-bca-16695","DOIUrl":"https://doi.org/10.15789/2220-7619-bca-16695","url":null,"abstract":"The search for predictors of the severe course of COVID-19 was relevant both during the pandemic and at the present time. The aim of the study was to analyze the relationship of cytokine levels in patients with EН before SARS-CoV-2 infection with the incidence of coronavirus pneumonia. Materials and methods. From the database of 290 patients with stage II EAG who have been under observation for 8–12 years with annual blood sampling to determine cytokine levels, COVID-19 survivors were selected (mild without pneumonia and moderate to severe, pneumonia CT 1–2, CT-3). Anamnestic levels of IL-1β, IL-1α, IL-1ra, IL-18, IL-18 BP, IL-37, IL-6, sIL-6r, M-CSF, VEGF-A, IL-34 and HMGB1) in the blood serum of patients with stage II EH were analyzed (method ELISA). The analysis of the obtained results was carried out using Stat Soft Statistica 13.5. Results and discussion. Patients with EH and COVID-19 with pneumonia (CT I-II) after SARS-CoV-2 infection 2–6 months before the infectious disease had significantly higher serum levels: IL-1α (p 0.05) and a decrease in IL-37 (p 0.001). During multivariate correlation analysis, a statistically independent relationship between an increase in the incidence of viral pneumonia in patients with stage II EН was confirmed only for IL-37 with a blood level of less than 60.2 pg/ml (regression coefficient — 2.21, standard error — 0.28, t criterion — 6.12, relative risk — 2.52, criterion Walda — 7.92, p = 0.006). When studying circadian rhythms of cytokine content in blood serum in patients of the analyzed groups, calculating the strength of correlations of anamnestic evening IL-37 levels in patients with stage II EР at 19.00–20.00 with the frequency of pneumonia against the background of SARS-CoV-2 infection, it has greater specificity and sensitivity (specificity — 0.75, sensitivity — 0.82) than morning concentrations. Considering that data on circadian rhythms were obtained in a limited number of patients, further monitoring is necessary, which is carried out by our scientific group. It should be noted that patients with essential hypertension are pathogenetically heterogeneous, including in terms of cytokine regulation. The study of this area will make it possible to personalize cytokine phenotypes of the disease and develop new methods for calculating the prognosis of both cardiovascular complications and features of the course of infectious diseases.","PeriodicalId":21412,"journal":{"name":"Russian Journal of Infection and Immunity","volume":"7 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141796777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-28DOI: 10.15789/2220-7619-voc-16749
M. G. Atazhakhova, G. A. Chudilova, L. Lomtatidze, E. A. Poezzhaev
Post-COVID syndrome (PCS) is characterized by long-term complications and conditions accompanied by neuroimmunoinflammation, and includes chronic fatigue syndrome (CFS) and cognitive disorders (CD), which are often associated with activation of chronic herpesvirus infections (HVI). Timely detection of symptoms and immunodiagnosis of PCS are a priority and are of undoubted interest. Objective: to clarify the levels of serum proand anti-inflammatory cytokines, alpha and gamma interferons in patients with post-COVID syndrome associated with confirmed activation of chronic herpesvirus infections. Patients (n = 60) aged from 18 to 65 years with complaints of manifestations of PCS associated with HVI were studied — the study group (SG). A survey was conducted using a modified scale-questionnaire to assess the severity of PCS symptoms in points from 0 to 4, real-time PCR of HVI (EBV, HSV1/2, VCH6, VCH8, CMV) in saliva and scrapings from the tonsils, determination of the level of IFNα and IFNγ, pro- (TNFα, IL-18, IL-1β, IL-6, IL-17A, IL-8) and anti-inflammatory (IL-4 and IL-10) cytokines in blood serum. Comparison group (CG) — 60 apparently healthy individuals. SG patients with mixed HVI with EBV dominance noted the most pronounced and persistent clinical manifestations of PCS, among which the leading place was occupied by longterm sensations of CFS and CD. A persistent multisystem inflammatory response was identified, confirmed by elevated levels of IL-6 and IL-17A, which caused severe PCS. In post-COVID period, hyperproduction of IL-1β was detected, which was accompanied by clinical manifestations of persistent neuroimmunoinflammation. At the same time, the identified deficiency of IFNα, IFNγ and dysregulatory disorders in the antiviral defense of the immune system in patients with PCS contributed to the activation of HVI. Data on the imbalance of proand anti-inflammatory cytokines in the SG were obtained, which confirms the presence of a persistent multisystem inflammatory reaction with dominance of persistent neuroimmunoinflammation, which causes severe PCS. An imbalance of the cytokine system with IFNα and IFNγ deficiency, associated with the activation of chronic HVI with EBV dominance in the post-COVID period, contributes to the development of neuroimmunoinflammation, which is accompanied by the leading clinical signs of PCS: CFS and CD.
{"title":"Variability of changes in proand antiinflammatory cytokines due to IFNα and IFNγ deficiency in patients with post-covid syndrome associated with activation of chronic herpes viral infections","authors":"M. G. Atazhakhova, G. A. Chudilova, L. Lomtatidze, E. A. Poezzhaev","doi":"10.15789/2220-7619-voc-16749","DOIUrl":"https://doi.org/10.15789/2220-7619-voc-16749","url":null,"abstract":"Post-COVID syndrome (PCS) is characterized by long-term complications and conditions accompanied by neuroimmunoinflammation, and includes chronic fatigue syndrome (CFS) and cognitive disorders (CD), which are often associated with activation of chronic herpesvirus infections (HVI). Timely detection of symptoms and immunodiagnosis of PCS are a priority and are of undoubted interest. Objective: to clarify the levels of serum proand anti-inflammatory cytokines, alpha and gamma interferons in patients with post-COVID syndrome associated with confirmed activation of chronic herpesvirus infections. Patients (n = 60) aged from 18 to 65 years with complaints of manifestations of PCS associated with HVI were studied — the study group (SG). A survey was conducted using a modified scale-questionnaire to assess the severity of PCS symptoms in points from 0 to 4, real-time PCR of HVI (EBV, HSV1/2, VCH6, VCH8, CMV) in saliva and scrapings from the tonsils, determination of the level of IFNα and IFNγ, pro- (TNFα, IL-18, IL-1β, IL-6, IL-17A, IL-8) and anti-inflammatory (IL-4 and IL-10) cytokines in blood serum. Comparison group (CG) — 60 apparently healthy individuals. SG patients with mixed HVI with EBV dominance noted the most pronounced and persistent clinical manifestations of PCS, among which the leading place was occupied by longterm sensations of CFS and CD. A persistent multisystem inflammatory response was identified, confirmed by elevated levels of IL-6 and IL-17A, which caused severe PCS. In post-COVID period, hyperproduction of IL-1β was detected, which was accompanied by clinical manifestations of persistent neuroimmunoinflammation. At the same time, the identified deficiency of IFNα, IFNγ and dysregulatory disorders in the antiviral defense of the immune system in patients with PCS contributed to the activation of HVI. Data on the imbalance of proand anti-inflammatory cytokines in the SG were obtained, which confirms the presence of a persistent multisystem inflammatory reaction with dominance of persistent neuroimmunoinflammation, which causes severe PCS. An imbalance of the cytokine system with IFNα and IFNγ deficiency, associated with the activation of chronic HVI with EBV dominance in the post-COVID period, contributes to the development of neuroimmunoinflammation, which is accompanied by the leading clinical signs of PCS: CFS and CD.","PeriodicalId":21412,"journal":{"name":"Russian Journal of Infection and Immunity","volume":"4 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141796864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-28DOI: 10.15789/2220-7619-pom-16865
A. P. Zherebtsov, I. V. Yakovleva, N. F. Gavrilova, N. A. Mikhailova
An important virulence factor in the pathogenesis of infections caused by Pseudomonas aeruginosa is flagellin: it serves as the main structural component of the bacterial flagellum and an acceptor for the TLR5 receptor of the innate immune system. Toll-like receptor 5 is able to bind bacterial flagellin and activate the anti-inflammatory transcription factor NF-kB through the adapter protein MyD88, which induces the production of anti-inflammatory cytokines. The inclusion of flagellin in recombinant proteins increased the ability to stimulate the production of anti-inflammatory cytokines and activate antigen-presenting cells. A number of experiments have shown that the use of flagellin as a molecular adjuvant in vaccines increases the expression of CD80, CD83, CD86 and MHC II molecules on the surface of dendritic cells, and also leads to an increase in the secretion of IFNγ and α-defensins by dendritic and NK cells; T cell proliferation and activation of antigen-specific cytotoxic T lymphocytes, as well as increased induction of antigen-specific IgG and IgA antibodies. Due to the natural and acquired resistance of P. aeruginosa to antibiotics, the available choice of antipseudomonas drugs is decreasing, and therefore the problem of developing effective therapeutic drugs to protect against this infection is of high medical and social importance. For this purpose, it seems promising to study the immunobiological properties of P. aeruginosa flagellin as a possible vaccine component. Based on this, in the Laboratory of Protective Antigens of the I. Mechnikov Research Institute of Vaccines and Sera, recombinant flagellin C (FliC) of P. aeruginosa was obtained, and its immunogenicity and protective properties were proven. However, the question of standardizing methods for screening and monitoring the resulting recombinant FliC protein remains open. To solve this issue, hybridomas producing monoclonal antibodies (mAb) of a given specificity were obtained, the basic immunochemical properties of mAbs were studied, and the possibility of using them as reagents in constructing a test system for identifying and standardizing the recombinant FliC protein upon its production was assessed. Purpose of the work: to obtain monoclonal antibodies to the recombinant flagellin C protein of P. aeruginosa; to study their basic immunochemical properties and to evaluate the possibility of using the recombinant FliC protein for screening and control.
铜绿假单胞菌感染发病机制中的一个重要毒力因子是鞭毛蛋白：它是细菌鞭毛的主要结构成分，也是先天性免疫系统 TLR5 受体的接受体。Toll 样受体 5 能够与细菌鞭毛蛋白结合，并通过适配器蛋白 MyD88 激活抗炎转录因子 NF-kB，从而诱导产生抗炎细胞因子。在重组蛋白中加入鞭毛蛋白，可提高刺激产生抗炎细胞因子和激活抗原递呈细胞的能力。大量实验表明，在疫苗中使用鞭毛蛋白作为分子佐剂可增加树突状细胞表面 CD80、CD83、CD86 和 MHC II 分子的表达，还可导致树突状细胞和 NK 细胞分泌更多的 IFNγ 和 α-防御素；T 细胞增殖和激活抗原特异性细胞毒性 T 淋巴细胞，以及诱导更多的抗原特异性 IgG 和 IgA 抗体。由于铜绿假单胞菌对抗生素的天然和后天耐药性，可供选择的抗假单胞菌药物越来越少，因此，开发有效的治疗药物来预防这种感染具有重要的医学和社会意义。为此，研究作为疫苗成分的铜绿假单胞菌鞭毛蛋白的免疫生物学特性似乎很有希望。在此基础上，I. Mechnikov 疫苗和血清研究所的保护性抗原实验室获得了铜绿微囊藻重组鞭毛蛋白 C (FliC)，并证明了其免疫原性和保护特性。然而，如何规范筛选和监测重组 FliC 蛋白的方法仍然是个问题。为了解决这个问题，我们获得了产生特定特异性单克隆抗体（mAb）的杂交瘤，研究了 mAb 的基本免疫化学性质，并评估了使用它们作为试剂构建检测系统的可能性，以便在重组 FliC 蛋白产生后对其进行鉴定和标准化。工作目的：获得铜绿假单胞菌重组鞭毛蛋白 C 蛋白的单克隆抗体；研究其基本免疫化学特性，并评估使用重组 FliC 蛋白进行筛选和控制的可能性。
{"title":"Preparation of monoclonal antibodies for detection of recombinant flagellin C from Pseudomonas Aeruginosa","authors":"A. P. Zherebtsov, I. V. Yakovleva, N. F. Gavrilova, N. A. Mikhailova","doi":"10.15789/2220-7619-pom-16865","DOIUrl":"https://doi.org/10.15789/2220-7619-pom-16865","url":null,"abstract":"An important virulence factor in the pathogenesis of infections caused by Pseudomonas aeruginosa is flagellin: it serves as the main structural component of the bacterial flagellum and an acceptor for the TLR5 receptor of the innate immune system. Toll-like receptor 5 is able to bind bacterial flagellin and activate the anti-inflammatory transcription factor NF-kB through the adapter protein MyD88, which induces the production of anti-inflammatory cytokines. The inclusion of flagellin in recombinant proteins increased the ability to stimulate the production of anti-inflammatory cytokines and activate antigen-presenting cells. A number of experiments have shown that the use of flagellin as a molecular adjuvant in vaccines increases the expression of CD80, CD83, CD86 and MHC II molecules on the surface of dendritic cells, and also leads to an increase in the secretion of IFNγ and α-defensins by dendritic and NK cells; T cell proliferation and activation of antigen-specific cytotoxic T lymphocytes, as well as increased induction of antigen-specific IgG and IgA antibodies. Due to the natural and acquired resistance of P. aeruginosa to antibiotics, the available choice of antipseudomonas drugs is decreasing, and therefore the problem of developing effective therapeutic drugs to protect against this infection is of high medical and social importance. For this purpose, it seems promising to study the immunobiological properties of P. aeruginosa flagellin as a possible vaccine component. Based on this, in the Laboratory of Protective Antigens of the I. Mechnikov Research Institute of Vaccines and Sera, recombinant flagellin C (FliC) of P. aeruginosa was obtained, and its immunogenicity and protective properties were proven. However, the question of standardizing methods for screening and monitoring the resulting recombinant FliC protein remains open. To solve this issue, hybridomas producing monoclonal antibodies (mAb) of a given specificity were obtained, the basic immunochemical properties of mAbs were studied, and the possibility of using them as reagents in constructing a test system for identifying and standardizing the recombinant FliC protein upon its production was assessed. Purpose of the work: to obtain monoclonal antibodies to the recombinant flagellin C protein of P. aeruginosa; to study their basic immunochemical properties and to evaluate the possibility of using the recombinant FliC protein for screening and control.","PeriodicalId":21412,"journal":{"name":"Russian Journal of Infection and Immunity","volume":"3 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141796982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-28DOI: 10.15789/2220-7619-mmc-16772
Irina D. Bulgakova, V. V. Zverev, E. O. Kravtsova, G. N. Usatova, D. A. Shoichet, E. A. Zadvornykh, A. A. Shumkina
Introduction. Today, prevalence of neurodegenerative diseases increases. In recent years, more studies have revealed a new knowledge about the role of microglia in the development of these diseases. Animal experiments showed that peripheral inflammation causes activation of microglia in brain. All this points to the essential role of the cells in the development of neurodegeneration. Under the influence of various factors, microglia can change the phenotype and participate in both repair and damage to brain cells. Chronic herpesvirus infection caused by HSV-1 is another known factor in the development of neurodegenerative pathology. However, the exact pathogenetic mechanisms are still unknown, nevertheless, studying the virus effect on microglia has great potential. The goal of our study in this connection was to assess the effect of HSV-1 on microglia polarization in mouse strain with normal susceptibility to this virus and in strain which is more resistant to the action of HSV-1. For this purpose, changes in the cytokine profile were detected. A comparison of interstrain differences in the expression of cytokine genes was also compared in control groups. Materials and methods. The study involved infecting C57BL/6 and BALB/c mice with herpes simplex virus type 1, an isolation of microglia was based on separation steps using a discontinuous gradient density, the cytokine profile was assessed by gene expression levels using a real-time reverse transcription PCR. To calculate the relative fold gene expression of samples the 2–ΔΔCt method was used. Statistical significance was determined using the Mann–Whitney U-test. Results. There were found no interstrain differences in cytokine gene expression in control groups of different mouse strains. At the same time, gene expression differed in the experimental groups: in BALB/c mice, the expression of genes for both pro-inflammatory and anti-inflammatory cytokines increased; in C57BL/6 mice, a slight increase in the expression of IL-1β genes was observed. Conclusion. The data indicate the formation of different microglial phenotypes after HSV-1 infection in different mouse strains. Apparently, in BALB/c mice there is a switch from the pro-inflammatory M1 phenotype of microglia to the anti-inflammatory M2 phenotype, while in C57BL/6 mice the attenuation of the infectious process occurs through a return to the original M0 phenotype.
{"title":"Mice microglia cytokine profile changes under the influence of HSV-1","authors":"Irina D. Bulgakova, V. V. Zverev, E. O. Kravtsova, G. N. Usatova, D. A. Shoichet, E. A. Zadvornykh, A. A. Shumkina","doi":"10.15789/2220-7619-mmc-16772","DOIUrl":"https://doi.org/10.15789/2220-7619-mmc-16772","url":null,"abstract":"Introduction. Today, prevalence of neurodegenerative diseases increases. In recent years, more studies have revealed a new knowledge about the role of microglia in the development of these diseases. Animal experiments showed that peripheral inflammation causes activation of microglia in brain. All this points to the essential role of the cells in the development of neurodegeneration. Under the influence of various factors, microglia can change the phenotype and participate in both repair and damage to brain cells. Chronic herpesvirus infection caused by HSV-1 is another known factor in the development of neurodegenerative pathology. However, the exact pathogenetic mechanisms are still unknown, nevertheless, studying the virus effect on microglia has great potential. The goal of our study in this connection was to assess the effect of HSV-1 on microglia polarization in mouse strain with normal susceptibility to this virus and in strain which is more resistant to the action of HSV-1. For this purpose, changes in the cytokine profile were detected. A comparison of interstrain differences in the expression of cytokine genes was also compared in control groups. Materials and methods. The study involved infecting C57BL/6 and BALB/c mice with herpes simplex virus type 1, an isolation of microglia was based on separation steps using a discontinuous gradient density, the cytokine profile was assessed by gene expression levels using a real-time reverse transcription PCR. To calculate the relative fold gene expression of samples the 2–ΔΔCt method was used. Statistical significance was determined using the Mann–Whitney U-test. Results. There were found no interstrain differences in cytokine gene expression in control groups of different mouse strains. At the same time, gene expression differed in the experimental groups: in BALB/c mice, the expression of genes for both pro-inflammatory and anti-inflammatory cytokines increased; in C57BL/6 mice, a slight increase in the expression of IL-1β genes was observed. Conclusion. The data indicate the formation of different microglial phenotypes after HSV-1 infection in different mouse strains. Apparently, in BALB/c mice there is a switch from the pro-inflammatory M1 phenotype of microglia to the anti-inflammatory M2 phenotype, while in C57BL/6 mice the attenuation of the infectious process occurs through a return to the original M0 phenotype.","PeriodicalId":21412,"journal":{"name":"Russian Journal of Infection and Immunity","volume":"7 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141796356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-28DOI: 10.15789/2220-7619-bop-16848
Yulia A. Li, M. N. Dmitrachenko, E. V. Markelova, I. B. Korolev, M. P. Kostinov, L. I. Bondar
In 2019, the COVID-19 pandemic began and changed the world. Coronavirus SARS-CoV-2 has caused widespread illness and death around the world. In this regard, vaccination become the most important tool for creating herd immunity. Our study analyzed the dynamics of pro- and anti-inflammatory cytokines and antibodies to SARS-CoV-2 in the blood serum of young patients before and after vaccination against COVID-19. The study group included 76 young men. Determination of IL-1β, IL-4, IL-6, IL-8, IL-10, IL-17, IFNγ, TNFα and IgM and IgG antibodies to COVID-19 in venous blood sera was carried out twice, by ELISA using the test systems of Vector-Best Company, Novosibirsk. The first blood samples were carried out before vaccination, the second — 1 month after vaccination against COVID-19. The results were processed using STATISTICA 8.0. The vaccinated people were monitored for 6 months after vaccination. Levels of indices before vaccination: IL-1β (5.6 pg/ml (Q₂₅–Q₇₅ = 3.1–14.2); IL-4 (1.02 pg/ml (Q₂₅–Q₇₅ = 0.75–1.28); IL-6 (27.8 pg/ml (Q₂₅–Q₇₅ = 7.1–59.9); IL-8 (29.9 pg/ml (Q₂₅–Q₇₅ = 19.51–32.14); IL-10 (4.47 pg/ ml (Q₂₅–Q₇₅ = 1.84–14.75); IL-17 (7.33 pg/ml (Q₂₅–Q₇₅ = 6.82–8.58); IFNγ (0.7 pg/ml (Q₂₅–Q₇₅ = 0.4–0.9); TNFα (3.9 pg/ml (Q₂₅–Q₇₅ = 2.2–6.4). Levels of indices after vaccination: IL-1β (1.6 pg/ml (Q₂₅–Q₇₅ = 1.4- 2.2); IL-4 (0.84 pg/ml (Q₂₅–Q₇₅ = 0.59–1.12); IL-6 (1.2 pg/ml (Q₂₅–Q₇₅ = 0.6–1.7); IL-8 (10.1 pg/ml (Q₂₅–Q₇₅ = 3.8–28.9); IL-10 (5.84 pg/ml (Q₂₅–Q₇₅ = 1–9.99); IFNγ (0.6 pg /ml (Q₂₅–Q₇₅ = 0.3–0.8); TNFα (0.6 pg/ml (Q₂₅–Q₇₅ = 0.3–1.9). Both before and after vaccination against SARS-CoV-2, different distributions of cytokine levels were identified with a downward trend, but despite this, strong correlations were observed between many of them, which indicates an increase in the tension of the immune system in response to vaccination. When calculating the ratio of pro- and anti-inflammatory cytokines, its two-fold decrease was revealed, which reflects a decrease in the levels of pro-inflammatory cytokines after vaccination. The level of IgG antibodies to COVID-19 exceeded the protective level: more than 14 times in 98% of subjects. Further research into the impact of SARS-CoV-2 vaccination on innate immunity will allow us to reconsider the current vaccination strategy and determine the best approach to preventing COVID-19.
{"title":"Balance of pro- and anti-inflammatory cytokines in young patients who passed active Immunization against SARS-CoV-2 during the COVID-19 Pandemic","authors":"Yulia A. Li, M. N. Dmitrachenko, E. V. Markelova, I. B. Korolev, M. P. Kostinov, L. I. Bondar","doi":"10.15789/2220-7619-bop-16848","DOIUrl":"https://doi.org/10.15789/2220-7619-bop-16848","url":null,"abstract":"In 2019, the COVID-19 pandemic began and changed the world. Coronavirus SARS-CoV-2 has caused widespread illness and death around the world. In this regard, vaccination become the most important tool for creating herd immunity. Our study analyzed the dynamics of pro- and anti-inflammatory cytokines and antibodies to SARS-CoV-2 in the blood serum of young patients before and after vaccination against COVID-19. The study group included 76 young men. Determination of IL-1β, IL-4, IL-6, IL-8, IL-10, IL-17, IFNγ, TNFα and IgM and IgG antibodies to COVID-19 in venous blood sera was carried out twice, by ELISA using the test systems of Vector-Best Company, Novosibirsk. The first blood samples were carried out before vaccination, the second — 1 month after vaccination against COVID-19. The results were processed using STATISTICA 8.0. The vaccinated people were monitored for 6 months after vaccination. Levels of indices before vaccination: IL-1β (5.6 pg/ml (Q₂₅–Q₇₅ = 3.1–14.2); IL-4 (1.02 pg/ml (Q₂₅–Q₇₅ = 0.75–1.28); IL-6 (27.8 pg/ml (Q₂₅–Q₇₅ = 7.1–59.9); IL-8 (29.9 pg/ml (Q₂₅–Q₇₅ = 19.51–32.14); IL-10 (4.47 pg/ ml (Q₂₅–Q₇₅ = 1.84–14.75); IL-17 (7.33 pg/ml (Q₂₅–Q₇₅ = 6.82–8.58); IFNγ (0.7 pg/ml (Q₂₅–Q₇₅ = 0.4–0.9); TNFα (3.9 pg/ml (Q₂₅–Q₇₅ = 2.2–6.4). Levels of indices after vaccination: IL-1β (1.6 pg/ml (Q₂₅–Q₇₅ = 1.4- 2.2); IL-4 (0.84 pg/ml (Q₂₅–Q₇₅ = 0.59–1.12); IL-6 (1.2 pg/ml (Q₂₅–Q₇₅ = 0.6–1.7); IL-8 (10.1 pg/ml (Q₂₅–Q₇₅ = 3.8–28.9); IL-10 (5.84 pg/ml (Q₂₅–Q₇₅ = 1–9.99); IFNγ (0.6 pg /ml (Q₂₅–Q₇₅ = 0.3–0.8); TNFα (0.6 pg/ml (Q₂₅–Q₇₅ = 0.3–1.9). Both before and after vaccination against SARS-CoV-2, different distributions of cytokine levels were identified with a downward trend, but despite this, strong correlations were observed between many of them, which indicates an increase in the tension of the immune system in response to vaccination. When calculating the ratio of pro- and anti-inflammatory cytokines, its two-fold decrease was revealed, which reflects a decrease in the levels of pro-inflammatory cytokines after vaccination. The level of IgG antibodies to COVID-19 exceeded the protective level: more than 14 times in 98% of subjects. Further research into the impact of SARS-CoV-2 vaccination on innate immunity will allow us to reconsider the current vaccination strategy and determine the best approach to preventing COVID-19.","PeriodicalId":21412,"journal":{"name":"Russian Journal of Infection and Immunity","volume":"2 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141796477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-28DOI: 10.15789/2220-7619-net-16602
A. Kazimirskii, J. Salmasi, G. Poryadin, M. Panina, A. E. Kim, L. S. Rogozhina
One of the important problems of medicine is the search for new reliable markers of inflammation that would allow us to determine the type of inflammatory process. The aim of the study was to identify specific markers of infectious and aseptic inflammation based on the analysis of morphological variants of neutrophil extracellular traps (NETs). The study included 26 patients with various nosological forms of inflammation in the abdominal cavity (12 with acute appendicitis, 8 with acute cholecystitis, 6 with a diagnosis of pancreatitis/ pancreonecrosis) after surgery. The study also included 20 patients with post-COVID and a group of 10 volunteers no clinical manifestations of the disease, but at the same time had contacts with flu patients. Neutrophils were isolated using gradient centrifugation. Fluorescence microscopies with the dye SYBR Green (JSC “Evrogen”, Russia) were used for NET visualization and counting. NETs in the morphological form of neutrophils web structure were found in the blood of surgical patients with acute appendicitis who had a favorable course of the postoperative period. In a group of volunteers who were exposed to influenza but did not have symptoms of an infectious disease, we also found neutrophils web structure. In all patients with abdominal inflammation complicated by abdominal abscess, in addition to neutrophil web structure, abnormal forms of NETs were recorded, in particular, NETs in the form of single filaments. In the post-COVID patients an absolute absence of neutrophilis web structure was revealed. In all post-COVID patients, NETs are found only in the form of single filaments. The results of subsequent experiments showed that collagen peptides are inducers of the formation of NETs in the form of single filaments. The detection of neutrophils web structure is a sign of an infectious inflammatory process. NETs in the morphological form of single filaments are markers of aseptic inflammation, as well as a sign of endothelial damage.
{"title":"Neutrophil extracellular traps as markers of infectious and aseptic inflammation","authors":"A. Kazimirskii, J. Salmasi, G. Poryadin, M. Panina, A. E. Kim, L. S. Rogozhina","doi":"10.15789/2220-7619-net-16602","DOIUrl":"https://doi.org/10.15789/2220-7619-net-16602","url":null,"abstract":"One of the important problems of medicine is the search for new reliable markers of inflammation that would allow us to determine the type of inflammatory process. The aim of the study was to identify specific markers of infectious and aseptic inflammation based on the analysis of morphological variants of neutrophil extracellular traps (NETs). The study included 26 patients with various nosological forms of inflammation in the abdominal cavity (12 with acute appendicitis, 8 with acute cholecystitis, 6 with a diagnosis of pancreatitis/ pancreonecrosis) after surgery. The study also included 20 patients with post-COVID and a group of 10 volunteers no clinical manifestations of the disease, but at the same time had contacts with flu patients. Neutrophils were isolated using gradient centrifugation. Fluorescence microscopies with the dye SYBR Green (JSC “Evrogen”, Russia) were used for NET visualization and counting. NETs in the morphological form of neutrophils web structure were found in the blood of surgical patients with acute appendicitis who had a favorable course of the postoperative period. In a group of volunteers who were exposed to influenza but did not have symptoms of an infectious disease, we also found neutrophils web structure. In all patients with abdominal inflammation complicated by abdominal abscess, in addition to neutrophil web structure, abnormal forms of NETs were recorded, in particular, NETs in the form of single filaments. In the post-COVID patients an absolute absence of neutrophilis web structure was revealed. In all post-COVID patients, NETs are found only in the form of single filaments. The results of subsequent experiments showed that collagen peptides are inducers of the formation of NETs in the form of single filaments. The detection of neutrophils web structure is a sign of an infectious inflammatory process. NETs in the morphological form of single filaments are markers of aseptic inflammation, as well as a sign of endothelial damage.","PeriodicalId":21412,"journal":{"name":"Russian Journal of Infection and Immunity","volume":"3 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141796983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-28DOI: 10.15789/2220-7619-sot-16685
E. Volosnikova, D. N. Shcherbakov, N. V. Volkova, T. I. Esina, A. V. Zaikovskaya, G. G. Shimina, E. D. Danilenko
To increase the effectiveness and immunogenicity of modern vaccines, especially subunit ones, it is required to use adjuvants. Polysaccharides, due to their safety and biocompatibility, are desirable candidates for the creation of vaccine adjuvants. The aim of our study was to develop a method for obtaining beta-Glucans from the yeast Saccharomyces cerevisiae cell wall, and evaluate their adjuvant properties. The high purity and non-toxicity of the resulting preparation was achieved by using enzyme complexes of cellulase and protease in combination with ultrasound (22 kHz) at the purification stage. The developed scheme allows for the yield of beta-Glucans up to 2 g from 100 g of the biomass of wet cells. The adjuvant properties of beta-Glucans were studied in 50 male BALB/c mice, weighing 16–18 g. Immunization was performed twice, with a 14-day interval, intramuscularly, 200 μl per animal. The recombinant receptor-binding domain (RBD) of the surface S protein of the SARS-CoV-2 virus (Wuhan-Hu-1 and B.1.617.2 (Delta)) was used as an antigen, at a dose of 50 μg per animal. A positive control group was administered with the antigen combined with aluminum hydroxide. As a negative control, mice injected with the saline solution were used. The titers of specific antibodies in the blood sera were determined by ELISA assays. RBD (Wuhan-Hu-1 and Delta), and S protein (Wuhan-Hu-1, Delta and Omicron) were used as antigens. The titers of virus-neutralizing antibodies were measured in neutralization tests using SARS-CoV-2 virus strains Wuhan-Hu-1, Delta (B.1.617.2) and Omicron (B.1.1.529). The results of the study have shown that beta-Glucans have the ability to enhance the production of specific and virus-neutralizing antibodies in mice immunized with RBD. The titers of specific and virus neutralizing antibodies are comparable to their levels in the group immunized with RBD and Al(OH)₃. It has been found in the experiments in white outbred ICR mice that the preparation belongs to practically non-toxic substances. Therefore, it can be concluded that the use of beta-Glucans could become a preferable alternative to the conventional adjuvants based on aluminum salts, being biocompatible, biodegradable and non-toxic substances of low labor-intensive production.
{"title":"Study of the adjuvant properties of beta-glucans from Saccharomyces Cerevisiae yeast","authors":"E. Volosnikova, D. N. Shcherbakov, N. V. Volkova, T. I. Esina, A. V. Zaikovskaya, G. G. Shimina, E. D. Danilenko","doi":"10.15789/2220-7619-sot-16685","DOIUrl":"https://doi.org/10.15789/2220-7619-sot-16685","url":null,"abstract":"To increase the effectiveness and immunogenicity of modern vaccines, especially subunit ones, it is required to use adjuvants. Polysaccharides, due to their safety and biocompatibility, are desirable candidates for the creation of vaccine adjuvants. The aim of our study was to develop a method for obtaining beta-Glucans from the yeast Saccharomyces cerevisiae cell wall, and evaluate their adjuvant properties. The high purity and non-toxicity of the resulting preparation was achieved by using enzyme complexes of cellulase and protease in combination with ultrasound (22 kHz) at the purification stage. The developed scheme allows for the yield of beta-Glucans up to 2 g from 100 g of the biomass of wet cells. The adjuvant properties of beta-Glucans were studied in 50 male BALB/c mice, weighing 16–18 g. Immunization was performed twice, with a 14-day interval, intramuscularly, 200 μl per animal. The recombinant receptor-binding domain (RBD) of the surface S protein of the SARS-CoV-2 virus (Wuhan-Hu-1 and B.1.617.2 (Delta)) was used as an antigen, at a dose of 50 μg per animal. A positive control group was administered with the antigen combined with aluminum hydroxide. As a negative control, mice injected with the saline solution were used. The titers of specific antibodies in the blood sera were determined by ELISA assays. RBD (Wuhan-Hu-1 and Delta), and S protein (Wuhan-Hu-1, Delta and Omicron) were used as antigens. The titers of virus-neutralizing antibodies were measured in neutralization tests using SARS-CoV-2 virus strains Wuhan-Hu-1, Delta (B.1.617.2) and Omicron (B.1.1.529). The results of the study have shown that beta-Glucans have the ability to enhance the production of specific and virus-neutralizing antibodies in mice immunized with RBD. The titers of specific and virus neutralizing antibodies are comparable to their levels in the group immunized with RBD and Al(OH)₃. It has been found in the experiments in white outbred ICR mice that the preparation belongs to practically non-toxic substances. Therefore, it can be concluded that the use of beta-Glucans could become a preferable alternative to the conventional adjuvants based on aluminum salts, being biocompatible, biodegradable and non-toxic substances of low labor-intensive production.","PeriodicalId":21412,"journal":{"name":"Russian Journal of Infection and Immunity","volume":"3 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141796981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-28DOI: 10.15789/2220-7619-ccr-16721
N. A. Arsentieva, O. K. Batsunov, N. Liubimova, V. V. Basina, E. Esaulenko, A. A. Totolian
Hepatitis B is an infectious disease resulting from infection with the hepatitis B virus. Chronic hepatitis B (CHB) is characterized by prolonged inflammation in the liver, the development of fibrosis, liver cirrhosis and hepatocellular carcinoma. Factors of the immune system play a critical role in the pathogenesis of CHB. Thanks to chemokines, immune cells migrate to the site of inflammation to implement their effector functions. The CX3CL1/Fractalkine chemokine is the only member of the CX3C family of chemokines with unique structural and functional properties. Its receptor CX3CR1 is expressed mainly on the surface of cytotoxic effector lymphocytes such as NK cells, TNK and cytotoxic T lymphocytes. The purpose of our study was to analyze the content of CX3CL1/Fractalkine in the blood plasma of patients with CHB and the analysis of this chemokine with liver fibrosis. The concentration of CX3CL1/Fractalkine was determined in the blood plasma of patients with CHB using a multiplex assay based on xMAP technology. Blood plasma from patients with chronic viral hepatitis C (CHC) and autoimmune liver diseases (AILD) was used as a comparison group. The control group consisted of healthy individuals. For statistical analysis of data, nonparametric statistics methods were used: Kruskal–Wallis test, Spearman correlation coefficient ROC-analysis. It was shown a reduced level of CX3CL1/Fractalkine in patients with CHB compared with the control group (p = 0.0003) and with the comparison groups of CHC (p 0.0001) and AILD (p = 0.0005). A reduced concentration of CX3CL1/Fractalkine was shown in the blood plasma of CHB patients with initial fibrosis (p = 0.0092) and severe fibrosis/cirrhosis (p = 0.0009), while in patients with severe fibrosis/cirrhosis, a significantly reduced level of this chemokine was established compared with the initial degree of liver fibrosis (p = 0.0081). Correlation analysis revealed a highly significant inverse relationship between the severity of liver fibrosis and the content of CX3CL1/Fractalkine in the blood plasma of patients with CHB (Spearman r = –0.33; p = 0.02). Thus, the chemokine CX3CL1/Fractalkine is included in the immunopathogenesis of CHB; its reduced content is characteristic only of CHB and does not change in other chronic liver diseases. It is involved in the processes of liver fibrosis during infection with the hepatitis B virus. The concentration of the chemokine CX3CL1/Fractalkine depends on the stage of liver fibrosis in CHB, and a decrease in the level of CX3CL1/Fractalkine in the blood plasma can serve as a negative factor in the development of CHB.
{"title":"The role of сhemokine CX3CL1/Fractalkine in chronic viral hepatitis B","authors":"N. A. Arsentieva, O. K. Batsunov, N. Liubimova, V. V. Basina, E. Esaulenko, A. A. Totolian","doi":"10.15789/2220-7619-ccr-16721","DOIUrl":"https://doi.org/10.15789/2220-7619-ccr-16721","url":null,"abstract":"Hepatitis B is an infectious disease resulting from infection with the hepatitis B virus. Chronic hepatitis B (CHB) is characterized by prolonged inflammation in the liver, the development of fibrosis, liver cirrhosis and hepatocellular carcinoma. Factors of the immune system play a critical role in the pathogenesis of CHB. Thanks to chemokines, immune cells migrate to the site of inflammation to implement their effector functions. The CX3CL1/Fractalkine chemokine is the only member of the CX3C family of chemokines with unique structural and functional properties. Its receptor CX3CR1 is expressed mainly on the surface of cytotoxic effector lymphocytes such as NK cells, TNK and cytotoxic T lymphocytes. The purpose of our study was to analyze the content of CX3CL1/Fractalkine in the blood plasma of patients with CHB and the analysis of this chemokine with liver fibrosis. The concentration of CX3CL1/Fractalkine was determined in the blood plasma of patients with CHB using a multiplex assay based on xMAP technology. Blood plasma from patients with chronic viral hepatitis C (CHC) and autoimmune liver diseases (AILD) was used as a comparison group. The control group consisted of healthy individuals. For statistical analysis of data, nonparametric statistics methods were used: Kruskal–Wallis test, Spearman correlation coefficient ROC-analysis. It was shown a reduced level of CX3CL1/Fractalkine in patients with CHB compared with the control group (p = 0.0003) and with the comparison groups of CHC (p 0.0001) and AILD (p = 0.0005). A reduced concentration of CX3CL1/Fractalkine was shown in the blood plasma of CHB patients with initial fibrosis (p = 0.0092) and severe fibrosis/cirrhosis (p = 0.0009), while in patients with severe fibrosis/cirrhosis, a significantly reduced level of this chemokine was established compared with the initial degree of liver fibrosis (p = 0.0081). Correlation analysis revealed a highly significant inverse relationship between the severity of liver fibrosis and the content of CX3CL1/Fractalkine in the blood plasma of patients with CHB (Spearman r = –0.33; p = 0.02). Thus, the chemokine CX3CL1/Fractalkine is included in the immunopathogenesis of CHB; its reduced content is characteristic only of CHB and does not change in other chronic liver diseases. It is involved in the processes of liver fibrosis during infection with the hepatitis B virus. The concentration of the chemokine CX3CL1/Fractalkine depends on the stage of liver fibrosis in CHB, and a decrease in the level of CX3CL1/Fractalkine in the blood plasma can serve as a negative factor in the development of CHB.","PeriodicalId":21412,"journal":{"name":"Russian Journal of Infection and Immunity","volume":"5 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141797017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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