Candidiasis is one of the most common fungal diseases that can pose a threat to life in immunodeficient individuals, particularly in its disseminated form. Not only fungal invasion but also fatal infection-related inflammation are common causes of systemic candidiasis. In this study, we investigated in vitro immunomodulatory properties of the antifungal pea defensin Psd1 upon Candida albicans infection. Using the real-time PCR, we showed that Psd1 inhibited the antimicrobial peptide HBD-2 and pro-inflammatory cytokines IL-1 and IL-8 downregulation at mRNA level in epithelium cells caused by C. albicans infection. By using the Caco-2/immune cells co-culture upon C. albicans infection and the multiplex xMAP assay, we demonstrated that this pathogenic fungus induced a pronounced host defense response; however, the cytokine responses were different in the presence of dendritic cells or monocytes. We revealed that Psd1 at a low concentration (2 µM) had a pronounced immunomodulatory effect on the Caco-2/immune cells co-culture upon fungal infection. Thus, we hypothesized that the pea defensin Psd1 might be an effective agent in the treatment of candidiasis not only due to its antifungal activity, but also owing to its ability to modulate a protective immune response upon infection.
An increase in the frequency of mycoses and spreading of multidrug-resistant fungal pathogens necessitates the search for new antifungal agents. Earlier, we isolated the novel defensin from lentil Lens culinaris seeds, designated as Lc-def, which inhibited the growth of phytopathogenic fungi. Here, we studied an antifungal activity of Lc-def against human pathogenic Candida species, structural stability of the defensin, and its immunomodulatory effects that may help to prevent fungal infection. We showed that Lc-def caused 50% growth inhibition of clinical isolates of Candida albicans, C. krusei, and C. glabrata at concentrations of 25–50 μM, but was not toxic to different human cells. The lentil defensin was resistant to proteolysis by C. albicans and was not cleaved during simulated gastroduodenal digestion. By using the multiplex xMAP assay, we showed for the first time for plant defensins that Lc-def increased the production of such essential for immunity to candidiasis pro-inflammatory cytokines as IL-12 and IL-17 at the concentration of 2 μM. Thus, we hypothesized that the lentil Lc-def and plant defensins in general may be effective in suppressing of mucocutaneous candidiasis due to their antifungal activity, high structural stability, and ability to activate a protective immune response.
According to the World Health Organization, every year about 1 million cases of purulent bacterial meningitis (PBM) are registered in the world, of which 200 thousand cases end in death. Bacterial meningitis is polyethiologic, which makes the task of determining the pathogen the main in the organization of epidemiological surveillance, treatment regimens, planning of preventive and anti-epidemic measures. The quality of laboratory diagnostics has a key influence on this. The true incidence of meningitis of different etiology can be altered at low-efficiency laboratory diagnostics. This work was carried out to assess the effectiveness of existing laboratory methods for the detection of PBM pathogens: Haemophilus influenzae, Streptococcus pneumoniae and Neisseria meningitidis; as a part of the programme on sentinel surveillance of invasive bacterial diseases (IBD) carried out by the WHO regional office for Europe in a number of countries in Europe (Ukraine, Belarus), Transcaucasia (Azerbaijan, Armenia, Georgia), Asia (Uzbekistan, Kyrgyzstan, Kazakhstan) in the period 2010-2017. 2893 samples of clinical material (CSF and blood) obtained from patients with the meningeal syndrome were studied by four diagnostic methods: cultural method, latex-agglutination test, immunochromatographic test (BinaxNOW), PCR (conventional and real-time), used to identify the following pathogens: Neisseria meningitidis, Streptococcus pneumoniae, Haemophilus influenzae. When identifying the causative agents of BM, PCR more effective than culture method is 5 times in detecting N. meningitidis; 3 times in the detection of S. pneumoniae; 4 times the detection of H. influenzae b. Latex-agglutination test and immunochromatographic test allow to increase the identification of pathogens of BM for N. meningitidis - by 35.6%; S. pneumoniae - by 67%; H. influenzae b - by 19.2%, it is possible to set them in the field and at the epidpoint if necessary. When working with clinical material from patients diagnosed with GBM, it is advisable for bacteriological laboratories to complement the culture method of microbiological diagnosis of latex-agglutination test, immunochromatographic test or PCR.
The aim of the work - to establish the interconnection and interdependence of toll-like mediated pathogenetic mechanisms of urogenital infection in pregnant women from the position of epigenomics. Using discriminant analysis in 89 patients with urogenital infection in pregnant women for the first time was established a reliable evidence-based relationship and interdependence between mucosal immunity, the severity of the infectious process, clinical manifestations, symptoms of miscarriage in the background of simultaneous development of the infectious process and pregnancy. For urgent delivery (infection), urgent childbirth (infection and clinical manifestation) and premature birth, mucosal immunity determines the severity of anti-infective resistance (with increasing mucosal immunity oppression of infectious process and clinical manifestations is logged , and its decrease increases the severity of infection process and clinical manifestations); the inhibition of mucosal immunity prevails over its hyperreaction (inhibition of mucosal immunity is determined by the physiological immunodepression in response to the development of pregnancy, as well as in response to herpes virus infection when activated); the severity of the infectious process depends on the severity of clinical manifestations and symptoms of miscarriage. During miscarriage mucosal immunity provides the pathophysiological course of infectious process and the clinical manifestations and development of symptoms of misacrriage; increasing levels of mucosal immunity to hyperreaction contributes to the development of symptoms of abortion and miscarriage; not registered mutual influence of oppression, mucosal immunity and its hyperreaction; the severity of the infectious process does not depend on the severity of clinical signs and symptoms of miscarriage. In urgent childbirth (infection), the oppression of mucosal immunity does not affect the severity of clinical manifestations, symptoms of abortion and the infectious process. In urgent or premature birth, and termination of pregnancy, the oppression of mucosal immunity affects the severity of clinical manifestations, the severity of the infectious process and the symptoms of abortion; the severity of clinical manifestations and the severity of the symptoms of abortion are interrelated. In urgent birth (infection) mucosal immunity overreaction affects the severity of clinical manifestations, symptoms of miscarriage and infection; in case of term and preterm labour overreaction mucosal immunity on the severity of infection and symptoms of abortion and does not affect the severity of clinical manifestations and at the termination of a pregnancy mucosal immunity on the severity of the infectious process and does not affect the severity of clinical signs and symptoms of abortion. The levels of mucosal immunity inhibition, its hyperreaction, clinical manifestations, symptoms of pregnancy termination and the severity of the infectious process do not depend on the type of herpes simplex virus. In the absence of infection with herpes simplex virus in patients with urogenital infections of pregnant women, there is no mutual influence and the relationship between the oppression of mucosal immunity and hyperreaction of mucosal immunity, the oppression of mucosal immunity prevails over its hyperreaction. With increasing mucosal immunity oppression, increased anti-infectious resistance of the body (the decreased activity of the infectious process), and with its decrease decreased (increased activity of the infectious process). Hyperreaction of mucosal immunity influenced the severity of pregnancy termination symptoms, clinical manifestations and infectious process, and also determined the severity of pregnancy termination symptoms. The severity of the infectious process and clinical manifestations influenced the symptoms of abortion. The severity of the infectious process did not affect the clinical manifestations. During infection with herpes simplex virus type I or type I and II on the background prevalence of oppression mucosal immunity over hyperreaction mucosal immunity, the presence of relationships between them, and the impact of mucosal immunity on the severity of the infectious process and the clinical manifestations increase mucosal immunity has been shown to decrease the severity of infection and clinical manifestations (reduction of anti-infective resistance), while reducing mucosal immunity the severity of infection and clinical manifestations increased. Hyperreaction of mucosal immunity influenced the severity of pregnancy termination symptoms and determined the severity of pregnancy termination symptoms. The severity of the infectious process and clinical manifestations influenced the symptoms of abortion. The severity of clinical manifestations reflects the severity of the infectious process. In type I and type II of pregnancy, the level of mucosal immunity determines the anti-infectious resistance of the body in urogenital infection of pregnant women. Inhibition of mucosal immunity and its hyperreactions are interrelated, have an impact on each other, as a result of their integral interaction, increasing the levels of mucosal immunity leads to a decrease in the severity of clinical manifestations and the infectious process, reducing the levels of mucosal immunity contributes to the manifestation of clinical manifestations, as well as increasing the severity of the infectious process. Hyperreaction of mucosal immunity affects the severity of symptoms of abortion, infection and clinical manifestations. The infectious process and clinical manifestations determine the severity of the symptoms of abortion. In type III and type IV of pregnancy course, there is no mutual influence of mucosal immunity oppression and its hyperreaction. The levels of indicators of mucosal immunity oppression and its hyperreaction are interrelated; the increase in the severity of mucosal immunity oppression is accompanied by a decrease in clinical manifestations and severity of the infectious process and vice versa. Hyperreaction of mucosal immunity affects the severity of symptoms of abortion, infection and clinical manifestations. The infectious process determines the severity of the symptoms of abortion and clinical manifestations, acting as a leading component of gestational complications in urogenital infection of pregnant women. In the III type of pregnancy course oppression of mucosal immunity does not affect the severity of symptoms of miscarriage. In the IV type of pregnancy course, the levels of mucosal immunity oppression prevail over the indicators of mucosal immunity hyperreaction, which is due to the integral interaction of physiological inhibition of immunological reactivity of the organism in response to pregnancy and inhibition of immunological reactivity of the organism, accompanying the activation of infectious process of viral genesis. Hyperreaction of mucosal immunity determines the symptoms of abortion.
TLR are providing a launch of an infectious process when a macroorganism contacts with pathogenic OM and their communities. During the chlamydial infection different levels of TLR-2 and TLR-4 activation depend on qualitative composition of microbial communities present on the mucosa of UGT. Activation of TLR-2 and TLR-4 gene expression is occurring more pronounced in response to pathogens of STI, OM and less pronounced during contact with normoflora. The highest levels of TLR gene expression correspond to the higher OM contamination degree of cervical canal, urethra and vagina. TLR-2 and TLR-4 gene expression is taking place in response to OM in vagina and to OM and STI in cervical canal and urethra. Increase of TLR-2 and TLR-4 expression into urethra, cervical canal, and vagina correlates with severity of clinical manifestations of UGC depending on a pathogen, as well as on pathogenicity of associates (pathogens of STI and OM). Diagnostic and prognostic significance of the TLR-2 and TLR-4 gene expression levels assessment during urogenital chlamydiosis in women is determined. The assessment of levels of TLR-2 and TLR-4 gene expressions in scraping material of the cervix and urethra of patients with urogenital chlamydial infection allows to distinguish chronic and acute forms of chlamydiosis (chronic urogenital chlamydiosis is diagnosed with levels of expression of TL-receptor-2 not more than 5 units and TL-receptor-4 not more than 5 units in scraping material from the urethra), as well as to reveal the beginning of chronization of an infectious process. During acute urogenital chlamydiosis reduction of the TLR-2 and TLR-4 gene expression levels along with direct methods of detecting the pathogen can indirectly indicate an eradication of chlamydia.
Ключевые слова TLR-рецепторы врождённого клеточного иммунитета, урогенитальные инфекции. инфицирование, клинические проявления. infections TLR-8 level above 28 is a predictor of pregnancy termination and miscarriage.
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