Russian Journal of Infection and Immunity

Natural killer (NK) cells are innate lymphocytes acting as the key effector cells capable of recognizing and eliminating infected and transformed cells without prior sensitization. Their role in antibacterial defense, inflammatory response regulation and modulation of reproductive processes has been attracting increasing attention. In this regard, of particular interest are opportunistic bacteria of the ESKAPE group (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp.) characterized by high virulence, a prominent potential for developing multiple antibiotic resistance, being a lead cause of severe nosocomial infections, especially in immunocompromised patients. Pathogens of the ESKAPE produce a wide range of cell wall structural components (lipopolysaccharides, peptide glycans, lipoteichoic acids, capsular polysaccharides) as well as secreted virulence factors (pore-forming toxins, proteases, superantigen-like proteins, extracellular membrane vesicles) that can directly modulate immune cell functional activity. This review systematizes current literature data regarding the mechanisms underlying interplay between products of ESKAPE pathogenic bacteria as well as NK cell receptor apparatus and effector functions. Intracellular signaling pathways (NF-κB, MAPK, JAK/STAT) activated upon binding of bacterial ligands to pattern recognition receptors (TLR2, TLR4, TLR9, NOD1/NOD2) and their impact on NK cell cytotoxic potential, cytokine secretion profile (IFNγ, TNFα, IL-1β), and survival are primarily delineated. In addition, the immunomodulatory mechanisms mediated by bacterial metabolites on dendritic cells and macrophages subsequently affecting NK cell activation are discussed as well. Understanding the complex network of molecular crosstalk between ESKAPE pathogen metabolites and NK cells is fundamental for developing novel immunotherapy strategies for drug-resistant infections, designing adjuvant drugs based on bacterial components as well as correcting immune disorders in critical conditions. Altogether, it opens up a new avenue to a personalized treatment approach for patients with severe nosocomial infections.

Human herpesviruses 6A and 6B (HHV6A, HHV6B) are ubiquitous pathogens with lifelong persistence in the human body. HHV6A/B infection often accompanies HIV infection, however, data on the interaction between the two viruses are contradictory. The discrepancy in study results on the influence of HHV6A/B on the course of HIV infection may be due to the molecular genetic variability of the betaherpesviruses. The aim of this work was to assess the molecular genetic diversity of HHV6A and HHV6B in HIV-infected adults in the Nizhny Novgorod region. Materials and methods. Blood leukocyte isolates from 138 HIV-infected patients (HIV(+)) and 68 HIV-uninfected (HIV(–)) individuals were studied. HHV6A/B species were identified by PCR with agarose gel electrophoresis. Nucleotide sequences of the U90A (206 bp) and U90B (431 bp) gene fragments were obtained by Sanger sequencing. The intra-species genovariant of the examined betaherpesviruses was determined based on signature nucleotide substitutions of the sequenced sequences and in accordance with the author’s classification. Results. HHV6A/B DNA was detected in 39% of HIV(+) and 46% of HIV(–) examined individuals. HHV6A (genovariant GV3a) was identified in one HIV(+) sample. The remaining samples from both groups contained HHV6B. In the group of HIV-infected patients, dominant genovariants GV1a, GV2b, and GV2e (~30% each) were evenly distributed, and the minor GV2a (7.3%) was also detected. In the group of clinically healthy virus carriers, genovariant GV2e predominated (72.4%), while GV1a and GV2b were less common. The likelihood of detecting GV2e decreased (OR = 0.18 (0.04; 0.76), p = 0.031), whereas that of for GV1a and GV2b variants increased (in both cases OR = 5.48 (1.31; 28.52), p = 0.016) in HIV(+) individuals compared to control group. Analyzing age structure for HHV6B genovariants showed that in HIV-infected patients, the diversity of genovariants declines with decreasing patient age. Сonclusion. The obtained results indicate the need to investigate the molecular genetic diversity of HHV6A and HHV6B for effective diagnosis and interpretation of findings in HIV-infected patients.

As part of the 365-day isolation experiment “SIRIUS-23” a relationship between hormone concentrations (estradiol and prolactin) and vaginal microbiota composition in four female participants was assessed. Vaginal swabs were collected 10–14 days before the start of isolation, on days 36, 64, 102, 123, 186, 256, and 339 of isolation study, and 10 days after its cessation. Blood estradiol and prolactin concentrations were measured using an enzyme-linked immunosorbent assay, while microbiological analysis included microbial culture on selective media and identification using MALDI-ToF MS, followed by statistical data processing using factorial and regression analysis, and nonparametric tests (Friedman, Mann–Whitney). The study revealed that estradiol concentrations decreased after the onset of isolation, reaching a minimum level on day 123 (p = 0.05), while prolactin demonstrated an upward trend on day 36, followed by a statistically significant decline on day 64. Factor analysis identified three main factors influencing the “hormone-bacteria” system: i) combined opportunistic microorganisms (OM) and prolactin; ii) included estradiol concentration and its antagonistic relation with some OM number; iii) mirrored competitive interplay between microorganisms. Estradiol concentration correlated positively with protective lactobacilli count (L. aginalis, L. jensenii, L. crispatus) and negatively with OM count, while prolactin concentration was more often positively associated with OM count (S. hominis, S. anginosus, C. amycolatum) and negatively with lactobacilli count. Regression analysis confirmed direct and inverse relationships, such as a positive association between prolactin concentration and E. coli count on day 64 and an inverse association between estradiol concentration and S. anginosus count. Stress factors (resource limitation, psychoemotional stress) exacerbated microbiota imbalance through decreased estradiol and increased prolactin level, which was particularly evident on day 102 of isolation, when OM count peaked in parallel with decreased lactobacilli count. The results highlight the key role for estradiol in maintaining vaginal microbiota balance and the opposite effect of prolactin associated with OM, which justifies a need to monitor hormonal levels and microbiota in women under extreme conditions (e.g., during space flights) and development of personalized probiotic strategies to minimize dysbiosis risks.

The skin microbiota contains non-diphtheria corynebacteria that can exhibit both pathogenic and beneficial properties. Genomic analysis of clinical isolates of Corynebacterium spp. will provide a more complete picture regarding their pathogenicity or positive effects. The aim of the study was to characterize the role of some clinical isolates of Corynebacterium spp. in shaping the skin microbiocenosis of healthy people based on assessing their genome. Materials and methods. Isolates of C. pseudodiphtheriticum SX1, C. glutamicum SX5, C. variable SX7 from the skin surface of conditionally healthy individuals were identified using mass spectrometry. Whole genome sequencing of bacterial strains and genomic analysis were performed. The virulence of Corynebacterium spp. strains was determined using the Galleria mellonellа larval model. The strains were deposited in the State Collection of Pathogenic Microorganisms and Cell Cultures “GKMP-Obolensk”, the genome sequences were placed in the GenBank database. Results. According to the phylogenetic analysis, the strains C. pseudodiphtheriticum SX1, C. glutamicum SX5 and C. variable SX7 form separate clades, and C. variable SX7 occupies a separate place, having a high phylogenetic proximity to mycobacteria. All isolates contain genes responsible for metabolism, stress protection, synthesis of amino acids, vitamins, and terpenes. Genes of the mntАBС system associated with resistance to hydrogen peroxide, superoxide radicals and the ability to use Mn²⁺ as an alternative cofactor in case of environmental iron deficiency were found only in C. pseudodiphtheriticum SX1. The ent genes regulating siderophore formation were found in the strains C. glutamicum SX5 and C. variable SX7. The spectrum of AMP resistance genes is wider in C. pseudodiphtheriticum SX1 and C. glutamicum SX5, and the genes presumably associated with AMP resistance are more common in C. variable SX7. Conclusion. C. pseudodiphtheriticum SX1, C. glutamicum SX5 and C. variable SX7 contain genes associated with metabolism, stress resistance, and the ability to survive in the human body. They lack true pathogenicity genes in the presence of polyfunctional genes associated with both metabolism and pathogenicity. Corynebacterium spp. isolates may produce useful substances (amino acids, vitamins, terpenes). This indicates their positive role in shaping human skin microbiocenosis.

Laboratory data are important for confirming diagnosis, assessing COVID-19 progression, and determining treatment measures. The aim of this study was to evaluate the associations of hematological, coagulation parameters, and systemic inflammatory markers with COVID-19 severity according to computed tomography data in hospitalized patients. Materials and methods. Clinical blood test parameters were assessed in 356 patients with COVID-19. Results. Patients with severe vs. minimal and moderate lung tissue damage have a significant increase in the absolute leukocyte count, the relative and absolute number of neutrophils, and a decrease in the relative number of monocytes and lymphocytes. These differences are also observed in patients with moderate vs. minimal lung tissue damage, except for the absolute leukocyte count. However, the latter as well as the relative number of neutrophils and lymphocytes in patients with minimal and moderate lung tissue damage, along with the absolute number of neutrophils and the relative number of monocytes in all patients were within the reference range. In COVID-19 patients with severe lung tissue damage, markers of systemic inflammation (neutrophil-lymphocytic index, platelet-lymphocytic index, systemic inflammatory response index, systemic inflammation index and cumulative systemic inflammation index) were higher than in those with the minimum and average volume, and the monocyte-lymphocyte index is higher than in those with the average volume of lung tissue damage. At the same time, in patients with minimal lesion volume, neutrophil-lymphocyte index and systemic inflammation index were at lower level, than in case of average volume of lung tissue lesion. Conclusion. The study revealed an association between the relative count of neutrophils and lymphocytes, neutrophil-lymphocyte ratio, systemic inflammation index, and systemic inflammatory response index, aggregate systemic inflammation index and severe COVID-19 disease based on computed tomography data. These biomarkers provide valuable information about systemic inflammation and immune system activity and can be detected using standard blood tests.

Seroepidemiological studies are essential for epidemiological surveillance of vaccine-preventable airborne infections prevented in children through using combination vaccines. The aim of the study was to assess post-vaccination immunity to diphtheria, pertussis, measles, rubella and mumps in children and adolescents living in the Republic of Karelia. Materials and methods. Results of seromonitoring in study groups of children and adolescents in the Republic of Karelia in 2019–2024 were retrospectively analyzed. Results. A high level of immunological protection was established only for diphtheria (0.7% seronegative among children 3–4 years and 1.0% among adolescents 16–17 years) and rubella (3–4 years — 1.7%, 9–10 years — 0.9%, 16–17 years — 2.2%). A total of 2.4% of children aged 3–4 years had no protective antibody titer to pertussis microbe in 2019–2021 and 67.9% in 2022–2024. The increase in the frequency of seronegative children coincided with increased incidence of infection and the beginning of using acellular vaccine. The agglutination test allows the detection of antibodies to the microorganism, but not to toxoid. The percentage of measles and mumps seronegative children aged 3–4 years was 9.1% and 19.5%, 9–10 years — 17.6% and 8.8%, among adolescents — 36.5% and 17.4%. An analysis of the epidemiological situation showed that seromonitoring data mirrored the state of post-vaccination immunity. The presence of antibodies to rubella in children seronegative to measles and mumps, and antitoxic antibodies to diphtheria at a high level in children seronegative to pertussis, excludes falsification of vaccination data or loss of vaccine immunogenicity due to violation of storage temperature conditions as potential causes of negative results. Conclusions. Our results demonstrate the importance of assessing antibodies to all simultaneously administered antigens and a need to expand a search for causes behind substantial level of seropositivity among children.

Background. Parenteral hepatitis B (HBV), C (HCV), and D (HDV) virus infections pose a global public health problem. It is critical to conduct epidemiological study for planning effective preventive and therapeutic interventions in the Kherson Region during post-crisis healthcare restoration. The study was aimed to comprehensively assess prevalence of population parenteral viral hepatitis markers in the Kherson Region, taking into account infection and vaccination status as well as sociodemographic characteristics. Materials and methods. A cross-sectional randomized study on the representative Kherson Region sample (N = 2806), stratified into 9 age groups was carried out. Anamnestic data on vaccination and former infections were collected. Serological markers (HBsAg, anti-HBc, anti-HBs, anti-HCV, anti-HDV) were quantitated by ELISA, verified further in case of positive HBsAg and anti-HCV results. Molecular markers (HBV DNA, HCV RNA, HDV RNA) were assessed by PCR, including a highly sensitive method for occult hepatitis B (OBI). Results. Prevalence of HBsAg-positive infection comprised 1.4%, peaking in the 40–49 age group (2.6%). Anti-HBc prevalence progressively increased with age (from 1.7% in under 18 to 21.5% in 70+). Total protective post-vaccination/infection immunity (anti-HBs ≥ 10 IU/L) was low (25.2%), peaking in children aged 1–5 years (58.9%), with sharp decline in adolescents and adults. A key finding: OBI (HBV DNA without HBsAg) dominated over manifest forms. HBV DNA was detected in 4.1% participants, of which 81.6% (3.3% total sample) were referred to OBI. Former iatrogenic interventions served as an OBI risk factor. Self-reported HBV vaccination coverage was 36.5%, but protective antibodies were found in only 31.6% of such vaccinated individuals. Anti-HCV prevalence was 4.1%, increasing with age; HCV RNA was detected in 1.2%. Anti-HDV antibody prevalence was 0.5%, not paralleled with HDV RNA detection. Conclusion. The Kherson Region shows a contradictory epidemiological situation: despite low HBV/HCV infection rates in the younger individuals, a critical issue is posed by insufficient population immunity due to low and ineffective HBV vaccination coverage, OBI dominance resulting in uncontrolled infection reservoir as well as association with iatrogenic interventions. These findings justify a need to strengthen routine immunization, implement catch-up vaccination, and introduce OBI screening in at-risk groups.

The Ob-Irtyshsky focus, which includes the Tyumen region is largest among Opisthorchis felineus invasion sites. The high intensity of invasion spreading in the outbreak underlies a high risk of infection often occurring with acute stage for the residents of the Tyumen region. The aim of this study was to evaluate the immunological parameters in patients with acute opisthorchiasis compared to healthy subjects. Ten patients at the clinic of the Tyumen Research Institute of Regional Infectious Pathology were examined with a diagnosis of acute opisthorchiasis. Immunological examination included lymphocyte phenotyping by flow cytometry. The concentration of immunoglobulins M, G, A, and E and cytokines IFNγ, IL-4, IL-8, IL-10 in blood serum was quantitated by enzyme immunoassay. Neutrophil absorbance was investigated in latex particle test (d = 1 μm). Neutrophil myeloperoxidase enzyme activity was measured spectrophotometrically, concentration of circulating immune complexes — by precipitation with PEG-6000 solution. In patients with acute opisthorchiasis, increased count of leukocytes, eosinophils, monocytes was detected; increased neutrophil scavenging and enzymatic activity; increased absolute number of CD3⁺ cells, absolute number of T-lymphocytes with CD3⁺HLA-DR⁺ marker, relative and absolute number of CD4⁺ cells were found as well. The concentration of total immunoglobulins G, A, M as well as circulating immune complexes and pro-inflammatory cytokine IL-8 were increased. A positive correlation between IL-8 levels and count of eosinophils, monocytes and percentage of natural killers was revealed in patients but not in control group. Patients have decreased levels of IFNγ and the cytokine IL-10. The level of IL-4 did not differ between patients with opisthorchiasis vs. control subjects. The correlation between IL-4 level and circulating immune complexes, count of eosinophils and natural killer cells was found in patients but not in control group. Thus, patients with acute opisthorchiasis were characterized by activated innate immune response as well as cellular and humoral arms of the adaptive immune response.