Pub Date : 2024-07-28DOI: 10.15789/2220-7619-tco-16612
P. Baikuzina, D. V. Gorbacheva, A. Apt, Mariya V. Korotetskaya
Genetic regulation of the host susceptibility to Mycobacterium tuberculosis (Mtb) and severity of tuberculosis (TB) infection remain incompletely investigated. Identification of particular genes and involved in TB control and immune reactions regulated by these genes is essential for our understanding of pathogenesis of the disease, discovery of drug targets and rational vaccine development. We have shown that mice of the B10.SM (H2ᵛ) strain are extremely TB susceptible; meanwhile, the general genome structure of this mouse strain and the H2ᵛ haplotype itself are poorly characterized. We selected a pool of Mit genetic markers differentiating B10.SM mice from Chr. 17-congenic mice of the B10 strain by the PCR products motility in the electrophoresis setting. TB susceptibility of B10 mice is much lower than that of B10.SM. In the model of infection triggered by two different dosed of Mtb (100 and 600 CFU per mouse) administered via respiratory tract we demonstrated that B10.SM mice have significantly shorter survival time and significantly higher lung mycobacterial multiplication compared to B10 mice. We demonstrated (intracellular staining and ELISA) that IFNγ production in the lungs of infected mice of the two strains corresponds well to their disease phenotypes. Thus, more resistant B10 mice possess significantly more lung IFNγ-positive CD4⁺ T cells and a higher level of IFNγ secretion. We have established (B10х B10.SM) F1 hybrids and demonstrated that the post-infection phenotypes of survival time, lung mycobacterial multiplication and IFNγ production in these mice are intermediate compared to parental mice. Thus, we deal with the genetic trait with incomplete dominance expression. These data were confirmed in F2 hybrids by segregation genetic analysis. To characterize the phenotype of B10.SM mice in more detail, we vaccinated these mice with the BCG vaccine before TB challenge. Vaccination significantly prolonged survival time, diminished mycobacterial multiplication in the lungs and the degree of lung tissue pathology. Thus, a high level of susceptibility to primary infection did not interfere with BCG vaccination efficacy. We intend to continue genetic and immunologic analyses of TB-hyper-susceptible B10.SM mice. Experimental data regarding the cause of extreme disturbances in protection against infection are prerequisite for our better understanding causality of the wide spectrum of TB manifestations in human populations, as well as for rational search for novel vaccines and medications against TB infection.
{"title":"The course of tuberculosis infection in hyper-susceptible mice carrying the H2ᵛ haplotype","authors":"P. Baikuzina, D. V. Gorbacheva, A. Apt, Mariya V. Korotetskaya","doi":"10.15789/2220-7619-tco-16612","DOIUrl":"https://doi.org/10.15789/2220-7619-tco-16612","url":null,"abstract":"Genetic regulation of the host susceptibility to Mycobacterium tuberculosis (Mtb) and severity of tuberculosis (TB) infection remain incompletely investigated. Identification of particular genes and involved in TB control and immune reactions regulated by these genes is essential for our understanding of pathogenesis of the disease, discovery of drug targets and rational vaccine development. We have shown that mice of the B10.SM (H2ᵛ) strain are extremely TB susceptible; meanwhile, the general genome structure of this mouse strain and the H2ᵛ haplotype itself are poorly characterized. We selected a pool of Mit genetic markers differentiating B10.SM mice from Chr. 17-congenic mice of the B10 strain by the PCR products motility in the electrophoresis setting. TB susceptibility of B10 mice is much lower than that of B10.SM. In the model of infection triggered by two different dosed of Mtb (100 and 600 CFU per mouse) administered via respiratory tract we demonstrated that B10.SM mice have significantly shorter survival time and significantly higher lung mycobacterial multiplication compared to B10 mice. We demonstrated (intracellular staining and ELISA) that IFNγ production in the lungs of infected mice of the two strains corresponds well to their disease phenotypes. Thus, more resistant B10 mice possess significantly more lung IFNγ-positive CD4⁺ T cells and a higher level of IFNγ secretion. We have established (B10х B10.SM) F1 hybrids and demonstrated that the post-infection phenotypes of survival time, lung mycobacterial multiplication and IFNγ production in these mice are intermediate compared to parental mice. Thus, we deal with the genetic trait with incomplete dominance expression. These data were confirmed in F2 hybrids by segregation genetic analysis. To characterize the phenotype of B10.SM mice in more detail, we vaccinated these mice with the BCG vaccine before TB challenge. Vaccination significantly prolonged survival time, diminished mycobacterial multiplication in the lungs and the degree of lung tissue pathology. Thus, a high level of susceptibility to primary infection did not interfere with BCG vaccination efficacy. We intend to continue genetic and immunologic analyses of TB-hyper-susceptible B10.SM mice. Experimental data regarding the cause of extreme disturbances in protection against infection are prerequisite for our better understanding causality of the wide spectrum of TB manifestations in human populations, as well as for rational search for novel vaccines and medications against TB infection.","PeriodicalId":21412,"journal":{"name":"Russian Journal of Infection and Immunity","volume":"5 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141797152","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-clb-16932
T. Kotomina, I. Sychev, A. Rak, P. Wong, A. V. Bazhina, I. Isakova-Sivak, L. Rudenko
Introduction. Influenza is a disease caused by a widespread virus with pandemic potential. Frequently, individuals vaccinated against seasonal influenza virus are still susceptible to the disease, indicating the need to improve the immunogenic potential of existing vaccines. To assess the efficacy of influenza virus vaccines, immune response only to a single viral antigen — hemagglutinin molecule, is taken into consideration. However, according to preclinical and clinical studies, neuraminidase (NA) stimulates cross-protective immunity, which is effective against not only homologous but also drifted variants of influenza A virus. Materials and methods. In the present study, we investigated the ability of previously selected conserved linear B-cell NA epitopes (SGYSGK, SWPDGK, EECSCYPK, VELIRGRK) to enhance the immunogenicity of an inactivated whole-virion influenza vaccine based on the model strain PR8 (iPR8). BALB/c mice were injected with iPR8 in combination with one of the peptides intramuscularly three times at two-week intervals. Blood samples were collected 14 days after the last immunization, after which the mice were challenged with heterosubtypic influenza viruses H1N1pdm09 and H3N2. Results. All immunized mice showed induction of H1N1 (PR8)-specific IgG antibodies two weeks after the third immunization. The group of mice immunized with the iPR8 vaccine preparation in combination with VELIRGRK peptide showed the most pronounced induction of IgG antibodies to the H6N1 reassortant strain, the NA of which corresponds to the iPR8 virus, indicating the ability of the NA peptide to stimulate the production of NA-specific antibodies. However, the antibodies produced after immunization were not capable to inhibit the NA enzymatic activity. Despite this, mice immunized with iPR8 in combination with anti-NA peptides showed a higher survival rate after infection with heterologous virulent influenza viruses: A/California/07/09 (H1N1pdm09) and A/Philippines/2/82 (H3N2) compared to the PBS and iPR8 groups. Conclusion. Thus, the study demonstrated the immune-potentiating effect of individual peptides corresponding to conservative linear epitopes of the NA molecule in combination with a standard inactivated influenza vaccine, which made it possible to improve the protective effect of the vaccine against heterosubtypic influenza viruses.
导言。流感是一种由广泛传播的病毒引起的疾病，具有大流行的潜力。接种过季节性流感病毒疫苗的人往往仍然容易感染这种疾病，这表明有必要提高现有疫苗的免疫原性。为了评估流感病毒疫苗的功效，只考虑了对单一病毒抗原--血凝素分子的免疫反应。然而，根据临床前和临床研究，神经氨酸酶（NA）可激发交叉保护性免疫，不仅对甲型流感病毒的同源变种有效，而且对漂移变种也有效。材料和方法。在本研究中，我们研究了先前选定的保守线性 B 细胞 NA 表位（SGYSGK、SWPDGK、EECSCYPK、VELIRGRK）增强基于模式毒株 PR8（iPR8）的全病毒灭活疫苗免疫原性的能力。对 BALB/c 小鼠肌肉注射 iPR8 和其中一种肽三次，每次间隔两周。最后一次免疫 14 天后采集血液样本，然后用异种亚型流感病毒 H1N1pdm09 和 H3N2 对小鼠进行挑战。结果所有免疫小鼠在第三次免疫两周后都出现了 H1N1（PR8）特异性 IgG 抗体。使用 iPR8 疫苗制剂与 VELIRGRK 肽联合免疫的小鼠组对 H6N1 重变异株（其 NA 与 iPR8 病毒相对应）的 IgG 抗体诱导效果最明显，这表明 NA 肽能够刺激产生 NA 特异性抗体。然而，免疫后产生的抗体并不能抑制 NA 酶的活性。尽管如此，使用 iPR8 和抗 NA 肽联合免疫的小鼠在感染异源毒性流感病毒后存活率更高：与 PBS 组和 iPR8 组相比，A/California/07/09（H1N1pdm09）和 A/Philippines/2/82（H3N2）组的存活率更高。结论因此，该研究证明了与 NA 分子保守线性表位相对应的单个肽与标准灭活流感疫苗联合使用时的免疫增强效应，这使得提高疫苗对异种亚型流感病毒的保护效果成为可能。
{"title":"Conserved linear B-cell peptides among the influenza A viral neuraminidases enhance the cross-protective potential of inactivated whole-virion influenza vaccine","authors":"T. Kotomina, I. Sychev, A. Rak, P. Wong, A. V. Bazhina, I. Isakova-Sivak, L. Rudenko","doi":"10.15789/2220-7619-clb-16932","DOIUrl":"https://doi.org/10.15789/2220-7619-clb-16932","url":null,"abstract":"Introduction. Influenza is a disease caused by a widespread virus with pandemic potential. Frequently, individuals vaccinated against seasonal influenza virus are still susceptible to the disease, indicating the need to improve the immunogenic potential of existing vaccines. To assess the efficacy of influenza virus vaccines, immune response only to a single viral antigen — hemagglutinin molecule, is taken into consideration. However, according to preclinical and clinical studies, neuraminidase (NA) stimulates cross-protective immunity, which is effective against not only homologous but also drifted variants of influenza A virus. Materials and methods. In the present study, we investigated the ability of previously selected conserved linear B-cell NA epitopes (SGYSGK, SWPDGK, EECSCYPK, VELIRGRK) to enhance the immunogenicity of an inactivated whole-virion influenza vaccine based on the model strain PR8 (iPR8). BALB/c mice were injected with iPR8 in combination with one of the peptides intramuscularly three times at two-week intervals. Blood samples were collected 14 days after the last immunization, after which the mice were challenged with heterosubtypic influenza viruses H1N1pdm09 and H3N2. Results. All immunized mice showed induction of H1N1 (PR8)-specific IgG antibodies two weeks after the third immunization. The group of mice immunized with the iPR8 vaccine preparation in combination with VELIRGRK peptide showed the most pronounced induction of IgG antibodies to the H6N1 reassortant strain, the NA of which corresponds to the iPR8 virus, indicating the ability of the NA peptide to stimulate the production of NA-specific antibodies. However, the antibodies produced after immunization were not capable to inhibit the NA enzymatic activity. Despite this, mice immunized with iPR8 in combination with anti-NA peptides showed a higher survival rate after infection with heterologous virulent influenza viruses: A/California/07/09 (H1N1pdm09) and A/Philippines/2/82 (H3N2) compared to the PBS and iPR8 groups. Conclusion. Thus, the study demonstrated the immune-potentiating effect of individual peptides corresponding to conservative linear epitopes of the NA molecule in combination with a standard inactivated influenza vaccine, which made it possible to improve the protective effect of the vaccine against heterosubtypic influenza viruses.","PeriodicalId":21412,"journal":{"name":"Russian Journal of Infection and Immunity","volume":"8 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141796577","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-cov-16632
Marina M. Zafranskaya, D. B. Nizheharodava, O. G. Shatova, I. I. Russkih, A. V. Velichko, M. I. Vanslau, S. F. Novitskaya, T. L. Denisevich, M. G. Kolyadko, E. Kurlyanskaya
Heart transplant patients are at an increased risk of COVID-19 infection adverse outcomes because of underlying immunosuppression and concomitant comorbidities. To date, all large-scale randomized controlled trials for various COVID-19 vaccines have excluded solid organ transplant recipients. Therefore, the efficacy and safety of coronavirus infection prevention using COVID-19 vaccines in transplant heart patients has not been sufficiently studied. In this research, the evaluation of virus-specific immunological reactions after vaccination (double Vero Cell vaccination and Sputnik Light booster vaccination) in heart transplant patients has been carried out. In vaccinated heart transplant individuals who did not have a history of COVID-19, starting from 4–6 months after the 2nd dose of the vaccine, an increase in antibodies to S protein level of was observed, while maintaining statistically significant differences for 9–12 months after vaccination (regardless of whether with or without booster vaccination). However, the concentration of antibodies remained low, and 37% of patients detected no antibodies. In vaccinated heart transplant individuals following the previous COVID-19 infection, as compared to seronegative patients, post-vaccination immunity is accompanied by maintaining a high level of virus-specific IgG antibodies to the S protein of the SARS-CoV-2 virus in the dynamics of the post-vaccination period with a statistically significant increase of these antibodies by 9–12 months after booster vaccination. The specific cellular response (according to the assessment of CD3⁺154⁺ and CD3⁺IFNγ⁺ TNFα⁺ cells) to the S protein of the SARS-CoV-2 virus remained low throughout the entire follow-up period, was recorded in 5–40% of heart transplant patients and statistically significant changes in the number of spikereactive lymphocytes were observed in patients with a history of COVID-19 by 4–6 months after administration of the 2nd dose of the vaccine. This, together with the results of the assessment of the humoral response, indicates a more pronounced post-vaccination immunity in patients with a hybrid immunity. While developing a methodology for assessing the risk and benefit of a vaccination strategy for individual heart transplant patients, clinical efficacy, ongoing monitoring of rare serious adverse events, and data on vaccine immunogenicity should be taken into account.
{"title":"Characteristics of virus-specific immunological reactions following COVID-19 vaccination in heart transplant recipients","authors":"Marina M. Zafranskaya, D. B. Nizheharodava, O. G. Shatova, I. I. Russkih, A. V. Velichko, M. I. Vanslau, S. F. Novitskaya, T. L. Denisevich, M. G. Kolyadko, E. Kurlyanskaya","doi":"10.15789/2220-7619-cov-16632","DOIUrl":"https://doi.org/10.15789/2220-7619-cov-16632","url":null,"abstract":"Heart transplant patients are at an increased risk of COVID-19 infection adverse outcomes because of underlying immunosuppression and concomitant comorbidities. To date, all large-scale randomized controlled trials for various COVID-19 vaccines have excluded solid organ transplant recipients. Therefore, the efficacy and safety of coronavirus infection prevention using COVID-19 vaccines in transplant heart patients has not been sufficiently studied. In this research, the evaluation of virus-specific immunological reactions after vaccination (double Vero Cell vaccination and Sputnik Light booster vaccination) in heart transplant patients has been carried out. In vaccinated heart transplant individuals who did not have a history of COVID-19, starting from 4–6 months after the 2nd dose of the vaccine, an increase in antibodies to S protein level of was observed, while maintaining statistically significant differences for 9–12 months after vaccination (regardless of whether with or without booster vaccination). However, the concentration of antibodies remained low, and 37% of patients detected no antibodies. In vaccinated heart transplant individuals following the previous COVID-19 infection, as compared to seronegative patients, post-vaccination immunity is accompanied by maintaining a high level of virus-specific IgG antibodies to the S protein of the SARS-CoV-2 virus in the dynamics of the post-vaccination period with a statistically significant increase of these antibodies by 9–12 months after booster vaccination. The specific cellular response (according to the assessment of CD3⁺154⁺ and CD3⁺IFNγ⁺ TNFα⁺ cells) to the S protein of the SARS-CoV-2 virus remained low throughout the entire follow-up period, was recorded in 5–40% of heart transplant patients and statistically significant changes in the number of spikereactive lymphocytes were observed in patients with a history of COVID-19 by 4–6 months after administration of the 2nd dose of the vaccine. This, together with the results of the assessment of the humoral response, indicates a more pronounced post-vaccination immunity in patients with a hybrid immunity. While developing a methodology for assessing the risk and benefit of a vaccination strategy for individual heart transplant patients, clinical efficacy, ongoing monitoring of rare serious adverse events, and data on vaccine immunogenicity should be taken into account.","PeriodicalId":21412,"journal":{"name":"Russian Journal of Infection and Immunity","volume":"4 12","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141796582","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-tso-16754
K. S. Fedorova, K. A. Abramovskikh, A. Savochkina, A. Minasova, M. A. Zotova, A. I. Samatova, D. Y. Nokhrin, K. V. Nikushkina
Bacterial vaginosis is one of the most common reproductive health problems in women. Lactobacillus spp. play a leading role in the vaginal biocenosis and provide local antimicrobial defense, but not all species are equally capable of protecting the vaginal ecosystem from pathogens. Diagnostic methods in practical healthcare do not allow identification of Lactobacillus spp. species, which limits the ability to comprehensively assess the status of the vaginal biocenosis. We conducted a study in which we compared microscopy data of the examined smear with the detection of Lactobacillus spp. and other microorganisms. The aim of the study was to evaluate the species composition of Lactobacillus spp. from the vagina depending on morphologic characteristics and composition of associated flora. The study included 64 conditionally healthy women of reproductive age from 18 to 35 years old. The study of species composition of the vaginal biocenosis and typing of lactobacilli was carried out by real-time PCR methods. The obtained results were processed using generally accepted methods of descriptive and ordinal statistics. During the study, it was found that the vaginal biocenosis was dominated by species of Lactobacillus spp. L. crispatus, L. vaginalis, L. iners and L. jensenii. L. johnsonii was rarely found, and L. acidophilus was not detected. Typing results showed that the vagina was more frequently colonized by more than one species of Lactobacillus spp. while a single species of Lactobacillus spp. was detected less frequently. A correlation was found between Lactobacillus spp. species and bacilli thickness. If thick bacilli are detected in gynecological smear microscopy, they belong to the species L. crispatus, which has high colonization resistance and is a factor in the stability of the vaginal biocenosis. If smear microscopy reveals thin bacilli, then these are species of L. iners and L. jensenii. These representatives of Lactobacillus spp. are not directly related to the dysbiotic state of the vagina, but may indicate the possible development of dysbiosis in the future.
细菌性阴道病是女性最常见的生殖健康问题之一。乳酸杆菌在阴道生物链中发挥着主导作用，提供局部抗菌防御，但并非所有菌种都能保护阴道生态系统免受病原体侵害。实际医疗保健中的诊断方法无法识别乳酸杆菌的种类，这限制了全面评估阴道生物enosis状况的能力。我们进行了一项研究，比较了检查涂片的显微镜数据和乳酸杆菌及其他微生物的检测结果。研究的目的是根据相关菌群的形态特征和组成，评估阴道中乳酸杆菌的种类组成。研究对象包括 64 名 18 至 35 岁的条件健康育龄妇女。通过实时 PCR 方法对阴道生物菌群的物种组成和乳酸杆菌的分型进行了研究。研究结果采用公认的描述性和顺序统计方法进行处理。研究发现，阴道生物菌群主要由 L. crispatus、L. vaginalis、L. iners 和 L. jensenii 组成。很少发现约翰逊乳杆菌，也没有检测到嗜酸乳杆菌。分型结果表明，阴道较常被多个乳杆菌属菌种定植，而检测到单一乳杆菌属菌种的情况较少。研究发现，乳酸杆菌种类与杆菌厚度之间存在相关性。如果在妇科涂片显微镜下检测到粗大的杆菌，它们属于L. crispatus菌种，该菌种具有很强的定植抵抗力，是阴道生物菌群稳定性的一个因素。如果涂片显微镜下发现的是稀薄的杆菌，则属于 L. iners 和 L. jensenii。这些乳酸杆菌属的代表与阴道的菌群失调状态没有直接关系，但可能预示着未来可能出现菌群失调。
{"title":"State of the vaginal biocenosis depending on the species diversity of lactobacilli","authors":"K. S. Fedorova, K. A. Abramovskikh, A. Savochkina, A. Minasova, M. A. Zotova, A. I. Samatova, D. Y. Nokhrin, K. V. Nikushkina","doi":"10.15789/2220-7619-tso-16754","DOIUrl":"https://doi.org/10.15789/2220-7619-tso-16754","url":null,"abstract":"Bacterial vaginosis is one of the most common reproductive health problems in women. Lactobacillus spp. play a leading role in the vaginal biocenosis and provide local antimicrobial defense, but not all species are equally capable of protecting the vaginal ecosystem from pathogens. Diagnostic methods in practical healthcare do not allow identification of Lactobacillus spp. species, which limits the ability to comprehensively assess the status of the vaginal biocenosis. We conducted a study in which we compared microscopy data of the examined smear with the detection of Lactobacillus spp. and other microorganisms. The aim of the study was to evaluate the species composition of Lactobacillus spp. from the vagina depending on morphologic characteristics and composition of associated flora. The study included 64 conditionally healthy women of reproductive age from 18 to 35 years old. The study of species composition of the vaginal biocenosis and typing of lactobacilli was carried out by real-time PCR methods. The obtained results were processed using generally accepted methods of descriptive and ordinal statistics. During the study, it was found that the vaginal biocenosis was dominated by species of Lactobacillus spp. L. crispatus, L. vaginalis, L. iners and L. jensenii. L. johnsonii was rarely found, and L. acidophilus was not detected. Typing results showed that the vagina was more frequently colonized by more than one species of Lactobacillus spp. while a single species of Lactobacillus spp. was detected less frequently. A correlation was found between Lactobacillus spp. species and bacilli thickness. If thick bacilli are detected in gynecological smear microscopy, they belong to the species L. crispatus, which has high colonization resistance and is a factor in the stability of the vaginal biocenosis. If smear microscopy reveals thin bacilli, then these are species of L. iners and L. jensenii. These representatives of Lactobacillus spp. are not directly related to the dysbiotic state of the vagina, but may indicate the possible development of dysbiosis in the future.","PeriodicalId":21412,"journal":{"name":"Russian Journal of Infection and Immunity","volume":"3 11","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141796872","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-sth-16743
Svetlana V. Kovaleva, V. N. Chapurina, L. Lomtatidze, D. E. Lyagusha, Yu. V. Teterin, N. K. Barova, K. I. Melkonyan
The study of dysregulatory disorders of the immune system underlying the immunopathogenesis of severe purulent-inflammatory diseases (PIDs) is important for development of new therapeutic tactics of restoring antibacterial defense. Acute peritonitis (AP) is a severe PID of the abdominal cavity, the course of which are dependent on the treatment, cytokine balance and adequate functioning of the immunity. Objective: to evaluate the modulating effects on the immune system and the levels of proinflammatory cytokines of the synthetic thymic hexapeptide, active substance of Imunofan, included in the complex postoperative treatment (CPOT) of immunocompromised children with local AP. Clinical and immunological examination of 20 immunocompromised children aged 5–12 years with local AP was carried out before (study group 1, SG1) and after (study group 1a, SG1a) CPOT including synthetic thymic hexapeptide (Arginyl-alpha-AspartylLysyl-Valyl-Tyrosyl-Arginine, НР), alongside 20 conditionally healthy children (comparison group, SG). The content of T and B lymphocytes, natural killer cells (NK), levels of serum pro-inflammatory cytokines IL-1β, IL-6, TNFα, IL-8, IL-18, phagocytic and microbicidal activity of neutrophils (NG) were assessed. In SG1, before treatment, a decrease in the number of T lymphocytes, T helpers, CTL-lymphocytes, NK and an increase in the level of B lymphocytes was revealed. Defects in the effector functions of NG were determined: impaired bacterial antigen killing and decreased NADPH oxidase activity. It was established that in case of AP in immunocompromised children, the cytokine profile is characterized by overproduction of studied proinflammatory and neutrophil-associated cytokines. After complex treatment including immunomodulatory therapy, there was a restoration of the content of T lymphocytes, T helper cells, TCTL lymphocytes, an increase in the number of NK and decrease in the level of B lymphocytes. In addition, regression of the levels of inflammatory, including neutrophil-associated, cytokines and emergence of effector functions of NG due to restoration of NADPH oxidases activity, was noted. Thus, the restoration of immunological parameters in AP leads to earlier regression of the purulent-inflammatory process in the abdominal cavity and to the absence of postoperative complications. The clinical and immunological effects of the immunomodulatory therapy program with inclusion of the drug based on HP determines the feasibility of its use in the postoperative period in immunocompromised children with local AP.
研究严重化脓性炎症疾病（PIDs）免疫发病机制背后的免疫系统调节紊乱，对于开发恢复抗菌防御的新疗法非常重要。急性腹膜炎（AP）是一种严重的腹腔化脓性炎症，其病程取决于治疗、细胞因子平衡和免疫系统的充分运作。目的：评估合成胸腺六肽（伊莫诺凡的活性物质）对免疫系统和促炎细胞因子水平的调节作用。对 20 名患有局部 AP 的 5-12 岁免疫力低下儿童（研究组 1，SG1）和 20 名条件健康儿童（对比组，SG）分别进行了 CPOT（包括合成胸腺六肽（精氨酰-α-天冬氨酰-赖氨酰-缬氨酰-酪氨酰-精氨酰，НР））之前（研究组 1a，SG1a）和之后（研究组 1a，SG1a）的临床和免疫学检查。对 T 和 B 淋巴细胞、自然杀伤细胞（NK）的含量、血清促炎细胞因子 IL-1β、IL-6、TNFα、IL-8、IL-18 的水平、中性粒细胞（NG）的吞噬和杀微生物活性进行了评估。在治疗前的 SG1 中，T 淋巴细胞、T 辅助淋巴细胞、CTL 淋巴细胞、NK 的数量减少，而 B 淋巴细胞的数量增加。研究还发现了 NG 的效应功能缺陷：细菌抗原杀伤力减弱和 NADPH 氧化酶活性降低。研究发现，免疫力低下儿童发生 AP 时，细胞因子谱的特点是所研究的促炎细胞因子和中性粒细胞相关细胞因子过度分泌。经过包括免疫调节疗法在内的综合治疗后，T 淋巴细胞、T 辅助细胞、TCTL 淋巴细胞的含量得到恢复，NK 数量增加，B 淋巴细胞水平下降。此外，由于 NADPH 氧化酶活性的恢复，炎症细胞因子（包括中性粒细胞相关细胞因子）的水平也有所下降，NG 的效应功能也有所显现。因此，AP 免疫学参数的恢复导致腹腔化脓性炎症过程提前消退，并避免了术后并发症。以 HP 为基础的药物免疫调节治疗方案的临床和免疫学效果决定了其在患有局部 AP 的免疫功能低下儿童术后使用的可行性。
{"title":"Synthetic thymic hexapeptide in the correction of alterations of antibacterial immune defense and normalization of the profile of proinflammatory cytokines in immunocompromized Children with local unlimited acute peritonitis","authors":"Svetlana V. Kovaleva, V. N. Chapurina, L. Lomtatidze, D. E. Lyagusha, Yu. V. Teterin, N. K. Barova, K. I. Melkonyan","doi":"10.15789/2220-7619-sth-16743","DOIUrl":"https://doi.org/10.15789/2220-7619-sth-16743","url":null,"abstract":"The study of dysregulatory disorders of the immune system underlying the immunopathogenesis of severe purulent-inflammatory diseases (PIDs) is important for development of new therapeutic tactics of restoring antibacterial defense. Acute peritonitis (AP) is a severe PID of the abdominal cavity, the course of which are dependent on the treatment, cytokine balance and adequate functioning of the immunity. Objective: to evaluate the modulating effects on the immune system and the levels of proinflammatory cytokines of the synthetic thymic hexapeptide, active substance of Imunofan, included in the complex postoperative treatment (CPOT) of immunocompromised children with local AP. Clinical and immunological examination of 20 immunocompromised children aged 5–12 years with local AP was carried out before (study group 1, SG1) and after (study group 1a, SG1a) CPOT including synthetic thymic hexapeptide (Arginyl-alpha-AspartylLysyl-Valyl-Tyrosyl-Arginine, НР), alongside 20 conditionally healthy children (comparison group, SG). The content of T and B lymphocytes, natural killer cells (NK), levels of serum pro-inflammatory cytokines IL-1β, IL-6, TNFα, IL-8, IL-18, phagocytic and microbicidal activity of neutrophils (NG) were assessed. In SG1, before treatment, a decrease in the number of T lymphocytes, T helpers, CTL-lymphocytes, NK and an increase in the level of B lymphocytes was revealed. Defects in the effector functions of NG were determined: impaired bacterial antigen killing and decreased NADPH oxidase activity. It was established that in case of AP in immunocompromised children, the cytokine profile is characterized by overproduction of studied proinflammatory and neutrophil-associated cytokines. After complex treatment including immunomodulatory therapy, there was a restoration of the content of T lymphocytes, T helper cells, TCTL lymphocytes, an increase in the number of NK and decrease in the level of B lymphocytes. In addition, regression of the levels of inflammatory, including neutrophil-associated, cytokines and emergence of effector functions of NG due to restoration of NADPH oxidases activity, was noted. Thus, the restoration of immunological parameters in AP leads to earlier regression of the purulent-inflammatory process in the abdominal cavity and to the absence of postoperative complications. The clinical and immunological effects of the immunomodulatory therapy program with inclusion of the drug based on HP determines the feasibility of its use in the postoperative period in immunocompromised children with local AP.","PeriodicalId":21412,"journal":{"name":"Russian Journal of Infection and Immunity","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141796442","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-eop-16804
N. D. Rasskazova, N. D. Abramova, T. D. Soshchenko, N. O. Kalyuzhnaya, E. A. Meremianina, M. N. Shatokhin, T. A. Zaitseva
Introduction. The mucous membrane of the upper respiratory tract is the entrance gate for a large number of infections, including the SARS-CoV-2 virus. That is why the main task of the immune system of the mucous membranes of the entrance gate of infection is to maintain respiratory function. High production of proinflammatory cytokines, which play a key role in the development of severe COVID-19 infection, leads to detrimental consequences for all body systems. Their long-term influence can not only aggravate chronic pathologies, but also significantly increase the recovery period, leading to a decrease in the quality of life of patients. Therefore, the purpose of this work is to study the expression of IL-18 and IL-33 genes at the level of the mucous membranes of the upper respiratory tract in patients who have had COVID-19 disease. Materials and methods. The present study involved patients who had moderate or severe COVID-19. The control group consisted of relatively healthy individuals. The expression levels of IL-18 and IL-33 were detected using RT-PCR. Results. During the entire period of rehabilitation after suffering from COVID-19, patients showed a tendency to increase the level of IL-18 expression at the level of the mucous membranes of the nasopharynx and oropharynx. The level of IL-33 production was also increased, but varied depending on the location and period of sample collection. Conclusion. This increase in the level of IL-18 during the rehabilitation period of patients after COVID-19 may be explained by the fact that the virus, by activating glia through olfactory receptor neurons, triggers a powerful immune response and promotes the production of a large number of pro-inflammatory cytokines. On the contrary, overexpression of IL-33 in the late stages of rehabilitation is most likely associated with its ability to restore barrier tissues of the mucous membranes of the upper respiratory tract. Thus, we can conclude that the virus promotes excessive production of pro-inflammatory cytokines, the amount of which increases maximally at the 6th month of rehabilitation after suffering from COVID-19.
{"title":"Expression of pro-inflammatory cytokines (IL-18, IL-33) at the level of the mucous membrane, the entry point of infection, in persons who have experienced COVID-19 disease","authors":"N. D. Rasskazova, N. D. Abramova, T. D. Soshchenko, N. O. Kalyuzhnaya, E. A. Meremianina, M. N. Shatokhin, T. A. Zaitseva","doi":"10.15789/2220-7619-eop-16804","DOIUrl":"https://doi.org/10.15789/2220-7619-eop-16804","url":null,"abstract":"Introduction. The mucous membrane of the upper respiratory tract is the entrance gate for a large number of infections, including the SARS-CoV-2 virus. That is why the main task of the immune system of the mucous membranes of the entrance gate of infection is to maintain respiratory function. High production of proinflammatory cytokines, which play a key role in the development of severe COVID-19 infection, leads to detrimental consequences for all body systems. Their long-term influence can not only aggravate chronic pathologies, but also significantly increase the recovery period, leading to a decrease in the quality of life of patients. Therefore, the purpose of this work is to study the expression of IL-18 and IL-33 genes at the level of the mucous membranes of the upper respiratory tract in patients who have had COVID-19 disease. Materials and methods. The present study involved patients who had moderate or severe COVID-19. The control group consisted of relatively healthy individuals. The expression levels of IL-18 and IL-33 were detected using RT-PCR. Results. During the entire period of rehabilitation after suffering from COVID-19, patients showed a tendency to increase the level of IL-18 expression at the level of the mucous membranes of the nasopharynx and oropharynx. The level of IL-33 production was also increased, but varied depending on the location and period of sample collection. Conclusion. This increase in the level of IL-18 during the rehabilitation period of patients after COVID-19 may be explained by the fact that the virus, by activating glia through olfactory receptor neurons, triggers a powerful immune response and promotes the production of a large number of pro-inflammatory cytokines. On the contrary, overexpression of IL-33 in the late stages of rehabilitation is most likely associated with its ability to restore barrier tissues of the mucous membranes of the upper respiratory tract. Thus, we can conclude that the virus promotes excessive production of pro-inflammatory cytokines, the amount of which increases maximally at the 6th month of rehabilitation after suffering from COVID-19.","PeriodicalId":21412,"journal":{"name":"Russian Journal of Infection and Immunity","volume":"5 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141796840","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-pat-16826
Evgeniya O. Khalturina, N. V. Garskova, A. D. Shemetova
Introduction. The problem of treating patients with respiratory allergopathology associated with recurrent infectious diseases, such as rARVI, frequent exacerbations of rCHVI, is becoming urgent. The presence of persistent inflammation and co-infection significantly complicates the treatment of immunocompromised patients with year-round allergic rhinitis (YAR) and necessitates the development of personalized programs, with the inclusion of immunomodulatory agents for restoring disorders in the immune system (IS) and interferon system (IFN). Materials and methods. The study group (SG) included 65 patients of both sexes aged 23–60 years, suffering from YAR associated with rARVI and rCHVI. The comparison group (CG) consisted of 50 healthy individuals, comparable in sex and age. All patients underwent standard physical, immunological and allergological examinations, including the use of serological (ELISA, ImmunoCUP), molecular genetic (PCR-RV) methods, FC, etc. Voluntary informed consent was obtained from all patients. The StatPlus computer program was used for statistical analysis. Results and discussion. In patients with YAR associated with rARVI and rCHVI, two variants of disorders in IS have been established, which are defined as pathological immunophenotypes (PIF). The PIF1 is characterized by a deficiency in the induced production of IFNα, a decrease in CD3⁻CD16⁺CD56+ EKKs, and a decrease in neutrophil granulocytes (NG). In the PIF2, along with a shortage of IFNα production, a decrease in EKKs is observed in combination with a decrease in CTLs, as well as a decrease in NGs. The clinical criteria for immunocompromising in this cohort of patients were studied. The severity of YAR symptoms was assessed by VAS. In order to correct the identified disorders in the IS and IFN system, complex personified IFN- and immunotherapy programs have been developed for each PIF, including prolonged local and systemic therapy with rIFNα2b in combination with antioxidants, as well as GMDP for patients of SG1, and for patients of SG2 — GMDP and hexapeptide. The high immunological and clinical efficacy of IFN- and immunotherapy was shown, which was expressed in the tendency to restore existing disorders, as well as in achieving control over the symptoms of YAR, with the possibility of reducing the volume of basic antiallergic pharmacotherapy.
{"title":"Personalized approach to immune system rehabilitation in patients with year-round allergic rhinitis suffering from recurrent ARVI and recurrent herpes virus infections","authors":"Evgeniya O. Khalturina, N. V. Garskova, A. D. Shemetova","doi":"10.15789/2220-7619-pat-16826","DOIUrl":"https://doi.org/10.15789/2220-7619-pat-16826","url":null,"abstract":"Introduction. The problem of treating patients with respiratory allergopathology associated with recurrent infectious diseases, such as rARVI, frequent exacerbations of rCHVI, is becoming urgent. The presence of persistent inflammation and co-infection significantly complicates the treatment of immunocompromised patients with year-round allergic rhinitis (YAR) and necessitates the development of personalized programs, with the inclusion of immunomodulatory agents for restoring disorders in the immune system (IS) and interferon system (IFN). Materials and methods. The study group (SG) included 65 patients of both sexes aged 23–60 years, suffering from YAR associated with rARVI and rCHVI. The comparison group (CG) consisted of 50 healthy individuals, comparable in sex and age. All patients underwent standard physical, immunological and allergological examinations, including the use of serological (ELISA, ImmunoCUP), molecular genetic (PCR-RV) methods, FC, etc. Voluntary informed consent was obtained from all patients. The StatPlus computer program was used for statistical analysis. Results and discussion. In patients with YAR associated with rARVI and rCHVI, two variants of disorders in IS have been established, which are defined as pathological immunophenotypes (PIF). The PIF1 is characterized by a deficiency in the induced production of IFNα, a decrease in CD3⁻CD16⁺CD56+ EKKs, and a decrease in neutrophil granulocytes (NG). In the PIF2, along with a shortage of IFNα production, a decrease in EKKs is observed in combination with a decrease in CTLs, as well as a decrease in NGs. The clinical criteria for immunocompromising in this cohort of patients were studied. The severity of YAR symptoms was assessed by VAS. In order to correct the identified disorders in the IS and IFN system, complex personified IFN- and immunotherapy programs have been developed for each PIF, including prolonged local and systemic therapy with rIFNα2b in combination with antioxidants, as well as GMDP for patients of SG1, and for patients of SG2 — GMDP and hexapeptide. The high immunological and clinical efficacy of IFN- and immunotherapy was shown, which was expressed in the tendency to restore existing disorders, as well as in achieving control over the symptoms of YAR, with the possibility of reducing the volume of basic antiallergic pharmacotherapy.","PeriodicalId":21412,"journal":{"name":"Russian Journal of Infection and Immunity","volume":"3 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141796873","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-lbm-16765
Z. R. Korobova, N. Liubimova, N. A. Arsentieva, M. S. Zhebeleva, E. I. Chernykh, V. V. Davletshina, V. A. Kashchenko, A. A. Totolian
Morality rates in COVID-19 are dependent on timely diagnosis. Therefore, studying the relationship between laboratory markers and the severity of disease is important. The first wave of COVID-19 associated with the spread of the original strain of SARS-CoV-2, showed higher mortality rates caused by cytokine storm. As the viral variant changed, a change in the disease course towards a less pronounced inflammatory reaction was observed. These changes affected major players of inflammation, cytokines. However, cytokines are not the only markers in the inflammatory response. The purpose of this work was to determine the significance of laboratory markers in inflammation: WBC, C-reactive protein, ferritin, fibrinogen, and D-dimer. The study included 227 patients with acute COVID-19 in the first 5–7 days from the onset of the disease from January 2021 to March 2022. When compared with reference, all groups were characterized by reduced absolute values of lymphocytes. Correlation analysis between the absolute value of lymphocytes and plasma cytokine concentrations also revealed statistically significant strong relationships with the level of the chemokine CCL22/MDC. Given that CCL22/MDC is an important component of lymphopoiesis, its low concentrations may indicate dysregulation of this process in COVID-19. In addition, we noted a positive correlation between the level of C-reactive protein and IL-6 in peripheral blood. IL-6 is a proinflammatory cytokine, and its elevated levels have been associated with the development of severe COVID-19. One of its functions is the induction of C-reactive protein, and this trend persists regardless of which variant causes COVID-19. We also noted positive correlations between the concentrations of fibrinogen and IL-18, ferritin and IL-6, IL-18. Both of these proteins are involved in inflammation along with cytokines. The literature provides data on the significance of these markers for determining the severity of COVID-19. There is evidence of a synergistic effect of ferritin and IL-18 against viral pathogens. Of interest was the negative correlation between plasma D-dimer levels and IFNα. At the same time, data on the role of the latter in thrombus formation processes are increasingly appearing in the literature.
{"title":"Laboratory blood markers in COVID-19 and their connection to Viral variant","authors":"Z. R. Korobova, N. Liubimova, N. A. Arsentieva, M. S. Zhebeleva, E. I. Chernykh, V. V. Davletshina, V. A. Kashchenko, A. A. Totolian","doi":"10.15789/2220-7619-lbm-16765","DOIUrl":"https://doi.org/10.15789/2220-7619-lbm-16765","url":null,"abstract":"Morality rates in COVID-19 are dependent on timely diagnosis. Therefore, studying the relationship between laboratory markers and the severity of disease is important. The first wave of COVID-19 associated with the spread of the original strain of SARS-CoV-2, showed higher mortality rates caused by cytokine storm. As the viral variant changed, a change in the disease course towards a less pronounced inflammatory reaction was observed. These changes affected major players of inflammation, cytokines. However, cytokines are not the only markers in the inflammatory response. The purpose of this work was to determine the significance of laboratory markers in inflammation: WBC, C-reactive protein, ferritin, fibrinogen, and D-dimer. The study included 227 patients with acute COVID-19 in the first 5–7 days from the onset of the disease from January 2021 to March 2022. When compared with reference, all groups were characterized by reduced absolute values of lymphocytes. Correlation analysis between the absolute value of lymphocytes and plasma cytokine concentrations also revealed statistically significant strong relationships with the level of the chemokine CCL22/MDC. Given that CCL22/MDC is an important component of lymphopoiesis, its low concentrations may indicate dysregulation of this process in COVID-19. In addition, we noted a positive correlation between the level of C-reactive protein and IL-6 in peripheral blood. IL-6 is a proinflammatory cytokine, and its elevated levels have been associated with the development of severe COVID-19. One of its functions is the induction of C-reactive protein, and this trend persists regardless of which variant causes COVID-19. We also noted positive correlations between the concentrations of fibrinogen and IL-18, ferritin and IL-6, IL-18. Both of these proteins are involved in inflammation along with cytokines. The literature provides data on the significance of these markers for determining the severity of COVID-19. There is evidence of a synergistic effect of ferritin and IL-18 against viral pathogens. Of interest was the negative correlation between plasma D-dimer levels and IFNα. At the same time, data on the role of the latter in thrombus formation processes are increasingly appearing in the literature.","PeriodicalId":21412,"journal":{"name":"Russian Journal of Infection and Immunity","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141797106","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-lto-16665
Mariia A. Salnikova, Yu. B. Lebedev
Infection is inconceivable without T cells. T cells not only eliminate virus-infected cells and participate in the formation of immunological memory, but also indirectly modulate the humoral response through the selection and maintenance of specific B cells. The T-cell receptor (TCR) recognizes processed antigen presented on the surface of cells in the MHC of one of two classes. Thus, the formed TCR repertoire reflects the history of encountered antigens through the prism of the specific organism with a particular set of MHC. To investigate changes in the TCR repertoire in response to acute viral infection, we utilized a yellow fever vaccination model. The yellow fever vaccine has been a benchmark for both safety and efficacy for over half a century. The vaccine is based on a live attenuated virus, allowing the study of the immune response under conditions closely to the viral infection. The yellow fever-specific T-cell response to immunodominant peptides presented on HLA-A02 is well studied, but experiments with HLA-A02-negative donors are still lacking. The aim of this study was to examine the dynamics of changes in the T-cell repertoire structure that occur in response to yellow fever vaccination in a donor without the HLA-A02 allele. We found that the overall T-cell response dynamics were similar to that in HLA-A02-positive donors: vaccination led to rapid expansion of yellow fever-reactive clones by day 14. Despite the absence of a known immunodominant epitope for HLA I alleles in this donor, the immune response also shifted towards CD8⁺ T cells, with increasing of the CD8⁺ clones fraction by day 53. The amino acid sequences of CDR3 TCRb yellow fever specific clones formed a stable cluster by CD4⁺ T cells, further confirming the presence of novel immunogenic epitopes.
没有 T 细胞，感染是不可想象的。T 细胞不仅能清除受病毒感染的细胞并参与免疫记忆的形成，还能通过选择和维持特异性 B 细胞间接调节体液反应。T 细胞受体（TCR）能识别呈递在 MHC 两类细胞之一表面的加工过的抗原。因此，形成的 TCR 复合物通过特定生物体与特定 MHC 组的棱镜反映了遇到抗原的历史。为了研究急性病毒感染时 TCR 复合物的变化，我们利用了黄热病疫苗接种模型。半个多世纪以来，黄热病疫苗一直是安全性和有效性的基准。该疫苗以减毒活疫苗为基础，可在接近病毒感染的条件下研究免疫反应。黄热病特异性 T 细胞对呈现在 HLA-A02 上的免疫显性肽的反应已被充分研究，但仍缺乏对 HLA-A02 阴性供体的实验。本研究的目的是研究没有 HLA-A02 等位基因的供体在接种黄热病疫苗后 T 细胞库结构的动态变化。我们发现，总体 T 细胞反应动态与 HLA-A02 阳性供体相似：接种疫苗后第 14 天，黄热病反应性克隆迅速扩大。尽管在该供体中不存在已知的 HLA I 等位基因免疫优势表位，但免疫反应也转向了 CD8⁺ T 细胞，到第 53 天，CD8⁺ 克隆的比例有所增加。CD4⁺ T细胞对CDR3 TCRb黄热病特异性克隆的氨基酸序列形成了一个稳定的簇，进一步证实了新型免疫原表位的存在。
{"title":"Longitudinal tracking of T-cell repertoire reveals long-lasting CD4⁺ yellow fever specific clone cluster","authors":"Mariia A. Salnikova, Yu. B. Lebedev","doi":"10.15789/2220-7619-lto-16665","DOIUrl":"https://doi.org/10.15789/2220-7619-lto-16665","url":null,"abstract":"Infection is inconceivable without T cells. T cells not only eliminate virus-infected cells and participate in the formation of immunological memory, but also indirectly modulate the humoral response through the selection and maintenance of specific B cells. The T-cell receptor (TCR) recognizes processed antigen presented on the surface of cells in the MHC of one of two classes. Thus, the formed TCR repertoire reflects the history of encountered antigens through the prism of the specific organism with a particular set of MHC. To investigate changes in the TCR repertoire in response to acute viral infection, we utilized a yellow fever vaccination model. The yellow fever vaccine has been a benchmark for both safety and efficacy for over half a century. The vaccine is based on a live attenuated virus, allowing the study of the immune response under conditions closely to the viral infection. The yellow fever-specific T-cell response to immunodominant peptides presented on HLA-A02 is well studied, but experiments with HLA-A02-negative donors are still lacking. The aim of this study was to examine the dynamics of changes in the T-cell repertoire structure that occur in response to yellow fever vaccination in a donor without the HLA-A02 allele. We found that the overall T-cell response dynamics were similar to that in HLA-A02-positive donors: vaccination led to rapid expansion of yellow fever-reactive clones by day 14. Despite the absence of a known immunodominant epitope for HLA I alleles in this donor, the immune response also shifted towards CD8⁺ T cells, with increasing of the CD8⁺ clones fraction by day 53. The amino acid sequences of CDR3 TCRb yellow fever specific clones formed a stable cluster by CD4⁺ T cells, further confirming the presence of novel immunogenic epitopes.","PeriodicalId":21412,"journal":{"name":"Russian Journal of Infection and Immunity","volume":"22 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141796682","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-omi-16717
G. S. Shepelkova, V. Evstifeev, V. V. Yeremeev
Tuberculosis, a disease caused by the bacterium Mycobacterium tuberculosis, is a major public health concern. Innate and adaptive immunity provide robust defense against pathogens. However, M. tuberculosis, which co-evolved with humans, has acquired many mechanisms to evade the immune response and ensure its intracellular existence and long-term survival within the host. Moreover, emerging evidence suggests that this secretive bacterium can alter expression of regulatory noncoding RNAs (including microRNAs), leading to dysregulation of biological processes underlying tuberculosis pathogenesis. For example, miR-222-3p has been shown to regulate the functional reprogramming of macrophages and is involved in the regulation of host innate immunity. Previously, we demonstrated the important role of miR-222-3p as a biological marker of tuberculosis activity. To confirm their biological targets and understand their role in the pathogenesis of tuberculosis, many research groups are working to establish functional relationships between miRNA expression under different conditions and their actual biological action using molecular biology and bioinformatics methods. In the present study, we demonstrated the effect of miR-222-3p overexpression on several functions of human macrophages of monocytic origin activated with M. tuberculosis antigens in in vitro culture. Specifically, we found that miR-222-3p overexpression significantly decreased IL-6 and IFNγ expression and increased IL-1β and cxcl10 expression in cultures of uninfected macrophages. Infected macrophages overexpressing miR-222-3p were characterized by increased NF-κB and IL-6 expression, as were infected macrophages without transfection. Another important finding was that miR-222-3p overexpression caused a small but significant increase in reactive nitrogen species production by infected macrophages, but did not affect their bacteriostatic activity against M. tuberculosis. Elucidating the functions of different microRNAs in regulating different pathogenic pathways in TB may lead to discovering new therapeutic targets. The detailed study of microRNAs that regulate immune-associated pathways will be useful for the design of miRNA mimetic molecules, either as inhibitors or as activators. Immune effects induced by miRNA drugs are currently a major challenge for miRNA therapeutics.
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