Репозиторий Университета

© Saint Petersburg Pasteur Institute. All rights reserved. The aim of the present systematic literature review is to summarize data on the role of TLRs in maintaining homeostasis of the female genitals, in maintaining the physiological development of pregnancy, provision of anti-infective resistance in pregnant women with intrauterine infection. The review substantiates the importance of TLRs of female genitals as a necessary and determining factor in the reaction to various changes in the environment, and also responsible for changes in metabolic, structural, or energy, in the maintenance of anti-infective resistance and homeostasis. As universal regulators of vital activity of organism TLRs in conjunction with other receptors of innate immunity provide maintaining the general reactivity and anti-infective resistance at the physiological level. In physiologically developing pregnancy in a background of immunosuppression in response to pregnancy TLRs during contact with infectious and non-infectious pathogens stimulate the production of nonspecific adaptive immunity factors (defensins, cathelicidins, histatines, etc.), which together with the non-specific innate factors lysozyme, complement, properdin, etc. support anti-infective resistance of the female genitals at a high level at the beginning of the infectious process. Possible violations of the development of pregnancy may be accompanied by changes in the response of TLRs to infectious and non-infectious factors until hyper-reaction, excessive inflammation or apoptosis, which requires adequate management of pregnancy. Was established the significance of the influence of pathogens of infectious and noninfectious origin in intrauterine infection indirectly through TLRs in the homeostasis of the organism, on the formation of breaches in anti-infective resistance at the organism and community level the identification of new pathophysiological and immunological pathogenetic mechanisms of development of pathological processes. IUI is a penetration of microorganisms into the tissues of fetus and it's infection. The inhibition of the functional activity of TLRs is accompanied by the direct effect of the pathogen on the tissues, and during hyper-reaction of TLRs to pathogens revealed a pronounced inflammatory response in the fetus. The level of expression of TLRs correlates directly with the severity of the process that can be considered as early markers of infection. Depending on the nature of the pathogen an increased expression of one or the other TLRs is observed. Explained the lack of symptoms, the possibility of atypical manifestations, the asymptomatic course of infection.

© 2018, SPb RAACI. The aim of this work was to study features of gene expression TLR2, TLR4, and TLR9 in the course of acute respiratory infection, depending on the time elapsing since the contamination, and dose of infection. The studies of in vivo models of acute respiratory infections caused by Gram-negative Klebsiella pneumoniae showed that, at infection dose of 104 CFU/ml, the TLR4 gene expression levels in epithelium of upper respiratory tract at 1, 3, 10 days were increased 30 times and more, complete elimination of the pathogen was observed at 3 days. At the dose of infection of 107 CFU/ml, persistence of the pathogen in upper respiratory tract was observed within a few days, accompanied by a significant increase in the level of TLR9 expression in epithelium of upper respiratory tract, and TLR4 levels in the lungs 1 day after infection, in parallel to elimination of the pathogen from the lower respiratory tract. Thus, the characteristic features of TLR4 and TLR9 gene expression in the upper respiratory tract may be considered a potential diagnostic and prognostic factors in evaluation of the course of acute respiratory infections caused by Klebsiella pneumoniae.

to investigate the myocardial expression of some structural proteins and markers of cellular proliferation and innate immunity for assessing their possible diagnostic and prognostic role in patients with chronic myocarditis. Subjects and methods. The investigation enrolled 23 patients (16 men; mean age, 52.0±12.4 years (range, 27 to 73) with various forms of noncoronarogenic myocardial injury who underwent right ventricular endomyocardial biopsy (n=4), intraoperative left ventricular biopsy (n=17) or autopsy (n=2). Prior to their morphological examination, the patients were divided into two groups: 1) 10 patients with dilated cardiomyopathy and presumptive myocarditis; 2) 13 patients with valvular heart disease, hypertrophic cardiomyopathy, myxoma, and chronic pulmonary thromboembolism, presumptively without myocarditis. Along with myocardial histological and immunohistochemical (IHC) examinations, the expression of vimentin, desmin, c-kit, Ki-67, and Toll-like receptors (TLR) 2 and 9 was determined. Polymerase chain reaction was used to identify whether herpes viruses of and parvovirus B19 genomes were present in the blood and myocardial samples; indirect ELISA was applied to estimate the blood level of antibodies against various cardiac antigens. Results. According to the histological findings, active/borderline lymphocytic myocarditis was diagnosed in all the patients (Group 1) and in 6 patients (Group 2) in conjunction with the underlying disease (only in 9 and 7 patients, respectively), viral genome was detected in the myocardium of 15 patients, including in 5 without morphological signs of myocarditis (parvovirus B19 (n=11), herpesvirus 6 (n=4), herpes simplex virus types 1 and 2 (n=1), Epstein-Barr virus (n=2), and cytomegalovirus (n=1)), and in the blood (n=4). A marked correlation was found between TLR2 and TLR9 expressions and the morphological pattern of active myocarditis in the absence of this correlation with the expression level of other studied markers. The expression level of TLR2 in patients with and without borderline myocarditis was 0 [0; 0,75] and in those with active myocarditis was 1.5 [1; 1,5] points; that of TLR9 was 2 [2; 2] and 4 [3; 4] points, respectively (p0.001). The expression of TLR2 and TLR9 in patients with borderline myocarditis was lower than in those without myocarditis (0 [0; 0] versus 0 [0; 1] and 2 [1,5; 2] versus 2 [2; 3] points), which can reflect cardiomyocyte destruction/depletion at later stages of the disease. There was also a close correlation between the expression level of TLR2 and that of TLR9 (r=0.824; p0.001) and with Ki-67 levels (r=-0.531 and r=-0.702; p0.01). There was also a correlation of the expression of the studied markers with viral persistence (desmin), the degree of myocardial dysfunction and cardiosclerosis (c-kit), which calls for further investigations. Conclusion. Determination of the myocardial expression level of TLR2 and TLR9 may serve as an immunohistochemical marker for myocarditis and preservation of its activity, which is especially valuable in patients with borderline forms. The marked expression of these markers for innate immunity may reflect both one of the mechanisms of genetic predisposition to myocarditis and its severe course and their secondary activation in the pathogenesis of the disease and is a potential target of therapy.

© 2018, SPb RAACI. The theory of polyetiological tumorigenesis is one of the most important theories of carcinogenesis. A great place in this theory is given to the role of inflammatory component, which is implemented via the factors of innate immunity. I.e., toll-like receptors (TLRs), chemokines and their receptors are related to innate immunity. Activation of TLRs may lead to regress or progression of cancer process. It is known that TLR3, TLR5, TLR7, TLR9 have the greatest anti-Tumor effect due to the dendritic cells (DCs)-mediated activation of type I T helpers, activation of M1-Type macrophages and Treg inhibition. Stimulation of TLR2 and TLR4 exerts an activating effect upon the tumor, by the MyD88 hyperactivation and secretion of IL-6 and TNFα, but exact mechanisms are not fully understood. In addition to TLRs, chemokines and their receptors have a great influence on the cancer development. It is shown that CCL2, CCL4, CCL17, CCL22 and CXCL12, which are secreted by cancer microenviroment, activate chemotaxis of tumor cells. It is also known that the chemokines activate CXCR4 and CCR7 (expressed by tumor cells) thus leading to metastasis. It is shown that there is an association between some gene polymorphisms of TLRs', chemokines and their receptors, and development of cancer. Thus, we may conclude that the role of TLRs and chemokines is important in oncogenesis. Further study of innate immunity factors influencing tumorigenesis are important for finding new approaches to cancer therapy and new potential vaccines against cancer.