Elizaveta P. Bystritskaya

This study examined Toll-like receptors (TLRs)/chemokine receptors (CCRs) gene expression levels in HIV-infected individuals at different stages of HIV infection. It has been demonstrated that in the advanced stages of HIV infection, aggravated by Mycobacterium tuberculosis (M. tuberculosis) infection, there was a significant increase in TLR2, TLR4, TLR7, and TLR9 expression levels (181-, 8.4-, 15-, and 3.4-fold, respectively), compared to the early stages of the disease, which also correlated with an increase in viral load. The advanced stages of HIV infection were also characterized by an increased CCR5 expression level (8.08-fold, p < 0.0001) on patients’ mononuclear cells, which was not observed in the early stages of the disease. A positive correlation was found between the enhanced levels of TLR2/TLR4 and CCR5 expression, which facilitates the entry of HIV-1 into the cell (r = 0.03564, p = 0.0423 for TLR2/TLR4; r = 0.3793, p = 0.0269 for CCR5). The advanced stages of HIV infection were characterized by a sharp increase in the expression levels of CXCR4 and CCR8 co-receptors which also play an important role in the entry of HIV-1 into the host cell (more than 537-fold, p = 0.0006, and 5000-fold, p = 0.004, respectively). At the advanced stages of HIV infection, a positive correlation was found between increased production of TLR and CCR and elevated expression of IL-12 and IL-18. These factors contribute to virus persistence and chronic immune activation observed in patients with opportunistic infections. Thus, the obtained data indicate that HIV-1 in the advanced stages of infection induces an increased TLRs and CCRs expression, which, together with enhanced viral production, leads to chronic inflammation and can contribute to tissue damage and exacerbate the disease’s progression.

Recent studies suggest that immune response to pathogens may vary depending on changes in hormone levels. Toll-like receptors (TLRs) are the key components of the innate immune system and play a crucial role in HIV infection. Given the significant genetic diversity of HIV-1, this study examined the effect of female sex hormones on the several TLR2, TLR4, and TLR9 expression in human peripheral blood mononuclear cells (PBLs) isolated from different female donors and infected with different variants of HIV-1 subtypes A6 and B. Thus, high doses of hormones upregulated the TLR2 and TLR9 expression in PBLs infected only with v1.A6, which also correlated with an increased viral load: by 3.8 times (p = 0.0033) when cells were treated with estradiol and by 4.4 times (p = 0.006) when treated with progesterone. Hormones did not modulate TLRs expression in the cells infected with subtype B, with the exception of one donor. In PBLs from this donor infected with the v1.B variant, hormones upregulated TLRs expression, which also correlated with the increased viral load (1.3-fold increase (p = 0.0036)). Hence, it was shown that gonadal steroids can play an important role in HIV-1 replication and immune response to a pathogen. Moreover, it was shown that different isolates of the same subtype may have distinct biological properties. The detected diversity in the TLRs expression in infected PBLs from different donors indicates that host genetics may also play an important role in HIV susceptibility.

We studied the effects of female sex hormones estradiol and progesterone on the expression of CCR5 and CCR8 co-receptor genes (that play an important role

The article assesses interconnections and interdependence between the immune status and invasion of human papilloma virus in patients with epithelial dysplasia of the mucous membrane of the mouth in order to improve efficiency of diagnostics and prognosis of these group of diseases

BACKGROUND: Phototherapy is one of the most effective methods in the treatment of psoriasis, but the mechanism of its action on innate immunity has not been studied. AIM: Investigation of the local expression profile of innate immunity factors in patients with psoriasis during phototherapy. MATERIALS AND METHODS: The study included 31 patients diagnosed with inpatient psoriasis vulgaris. The material for the study was obtained from areas of affected and unaffected skin. Patients with vulgar psoriasis received a course of UVB-311 nm phototherapy lasting from 5 to 7 weeks with a total dose of 35.2 to 44.6 J/cm2. There were 30 healthy people in the control group. Gene expression analysis was performed before treatment and at the end of the phototherapy course. The data obtained were statistically processed. RESULTS: According to the results of the study, gene expression data were obtained: for example, increased expression of the TLR2 and TLR9 genes was observed in the main group after treatment, as well as in samples of unaffected skin from patients. The increased level of the TLR4 gene expression was registered in unaffected skin samples from patients with psoriasis. The expression of the β-defensin 1 gene was elevated in unaffected skin and post-treatment skin. For the cathelicidin gene, there is a difference between the groups of affected and unaffected skin samples before treatment. The expression level of the IL-13 gene was higher before treatment. CONCLUSION: The revealed local imbalance of factors of innate immunity can lead to a more severe course of the disease. The course of phototherapy leads to normalization of the expression profile of receptor and effector molecules of innate immunity, which leads to a stable positive clinical effect.

Psoriasis is an immune-mediated autoimmune inflammatory skin disease with a prevalence of 2 to 3% worldwide. In the psoriasis development and pathogenesis an important role is played by disorders in the immune system. Disruption of the innate and adaptive immune response mechanisms with the involvement of keratinocytes leads to the initiation and maintenance of inflammation. Immune reactions are activated in the skin, in which various cells participate (macrophages, dendritic cells, mast cells, innate immune lymphoid cells, melanocytes, keratinocytes, Langerhans cells and γδT cells; T and B cells; epithelial endothelial and stromal cells of the skin), each of which expresses pattern recognition receptors that respond to pathogens and cell damage itself. Many of these receptors, in particular toll-like receptors and NOD-like receptors play an important role in the pathogenesis of psoriasis. The associated innate receptors signaling cascades that activate in the skin cells may become potential targets for the treatment of this disease. To date, there are several approved drugs for biological therapy of psoriasis. The study of the role of the innate immune cells receptors in inflammatory skin pathologies requires further exploration and new developments.

Atopic dermatitis (AD) is a genetically determined chronic inflammatory skin disease characterized by itching, relapsing course, age-related features of the lesion morphology and localization. The etiological factors contributing to the development of AD are: allergic reactions, inflammatory reactions in the skin, leading to a barrier disfunction, the affect and interaction of genetic and environmental factors. Epigenetic mechanisms also play a key role in immune regulation. The aim of this work is to study the genome-wide methylation profile in the skin of children with AD in the acute stage, as well as to determine changes in the expression level of immune response genes associated with common signaling pathways during therapy. Whole-genome sequencing was conducted to examine methylation in the skin samples from AD patients and controls. The stages of bioinformatics data processing were carried out. Changes in the expression levels of the TLR2, TLR9, IL4, IL13, CAMP, and DEFB1 genes before and after treatment were carried out using RT-PCR-RT on samples of mononuclear blood cells. When comparing samples from patients with AD and healthy children, changes were shown in the methylation of 2364 regions of genomic DNA with their corresponding specific genes. Among the identified genes, those related to processes associated with the pathogenesis of AD were selected. At the next stage, changes in the expression of the described immunity factors (TLR2, TLR9, IL-4, IL-13, DEFB1, CAMP) were assessed over time according to the type of treatment. For this purpose, patients were divided into 2 groups depending on the prescription of systemic therapy. Three months after treatment, the level of expression for all studied immune factors decreased. However, a significant decrease in expression for almost all parameters (except for the DEFB1 gene) was recorded in the group in which systemic therapy (dupilumab) was used in addition to topical treatment. At the same time, the SCORAD index after treatment improved by an average of 63% and amounted to 17±6.0 points. Thus, systemic therapy aimed at suppressing signaling of IL-4 and IL-13 cytokines indirectly leads to normalization of the expression levels of innate immune factors. Studying the regulation of molecular genetic mechanisms of immunity involved in the processes of inflammation in AD helps to clarify the immunopathogenesis of this disease, determine diagnostic markers and targets for drug therapy.

More than 50% of all people living with HIV worldwide are women. Globally, HIV/AIDS is the leading cause of death among women aged 15 to 44. The safe and effective methods of hormonal contraception are an essential component of preventive medical care in order to reduce maternal and infant mortality. However, there is limited knowledge regarding the effect of hormones on the rate of viral replication in HIV infection, especially non-B subtypes. The goal of the present work was to study in vitro how the female hormones β-estradiol and progesterone affect the replication of the HIV-1 subtypes A6, CRF02_AG, and B. The findings show that high doses of hormones enhanced the replication of HIV-1 sub-subtype A6 by an average of 1.75 times and the recombinant variant CRF02_AG by 1.4 times but did not affect the replication of HIV-1 subtype B. No difference was detected in the expression of CCR5 and CXCR4 co-receptors on the cell surface, either in the presence or absence of hormones. However, one of the reasons for the increased viral replication could be the modulated TLRs secretion, as it was found that high doses of estradiol and progesterone upregulated, to varying degrees, the expression of TLR2 and TLR9 genes in the PBMCs of female donors infected with HIV-1 sub-subtype A6.