Показатели врожденного иммунитета при общей вариабельной иммунной недостаточности и X-сцепленной агаммаглобулинемии 1 Федеральное государственное бюджетное учреждение «Государственный научный центр «Институт иммунологии» Федерального медико-биологического агентства

2021 1. Введение В клетках иммунной системы, как и в любых других клетках, протекает обмен веществ, лежащий в основе всех остальных биологических процессов.Совокупность обменных процессов, влияющая на функцию клеток иммунной системы, называется иммунометаболизмом.Активация различных типов клеток иммунной системы, как правило, требует резкого увеличения анаболизма.Так, для выработки регуляторных и эффекторных белковых молекул (цитокинов, антител, антимикробных белков и пептидов) необходимо возрастание синтеза белка

We performed a simultaneous analysis of cytokine expression and metabolic reprogramming of macrophages upon combined stimulation of NOD1 and TLR4 receptors of innate immunity. NOD1 and TLR4 agonists boosted main parameters of glycolysis (extracellular acidification rate, glucose consumption, lactate release). However, changes of these parameters upon combined stimulation were not greater than those induced by stimulation of each individual receptor. At the same time, combined stimulation synergistically induced pro-inflammatory cytokine production and mRNA expression at relatively late time points (4–9 hours) after addition of agonists. In all, metabolic reprogramming may support synergistic induction of cytokines upon combined NOD1 and TLR4 stimulation; however, the origin of this synergy is in the synergistic induction of cytokine gene expression.

Аэробный гликолиз не играет незаменимой роли в продукции провоспалительных цитокинов дендритными клетками 1 Федеральное государственное бюджетное учреждение «Государственный научный центр «Институт иммунологии» Федерального медико-биологического агентства, 115522, г.Москва, Российская Федерация 2 Федеральное государственное бюджетное образовательное учреждение высшего образования «Московский государственный университет имени М.В.Ломоносова», 119991, г.Москва, Российская Федерация 3 Федеральное государственное автономное образовательное учреждение высшего образования Российский научный исследовательский медицинский университет им.Н.И.Пирогова Министерства здравоохранения Российской Федерации, 119997, г.Москва, Российская Федерация 4 Федеральное государственное бюджетное учреждение «Национальный медицинский исследовательский центр онкологии им

We provide the fi rst characterization of glucose and energy metabolism rearrangements in human macrophages upon their activation with a NOD1 receptor agonist (N-acetyl-D-muramyl-L-alanylD-isoglutamyl-meso-diaminopimelic acid, or M-triDAP) in comparison with the eff ects of a TLR4 agonist, lipopolysaccharide (LPS). We demonstrate possibilities of modulation of cytokine production by macrophages using glycolysis inhibitors.

— Polypeptide SE-33 (SETRPVLNRLFDKIRQVIRKFEKGIKEKSKRFF), which is a retro analog of natural antimicrobial protein cathelicidin LL-37 (LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES), was synthesized by the method of solid-phase peptide synthesis. Similar to the natural peptide, polypeptide SE-33 forms an amphipathic alpha helix but has an inverted amino acid sequence compared to cathelicidin. It has been shown the physicochemical properties of polypeptide SE-33 are similar to those of the natural compound. In vitro experiments have shown that polypeptide SE-33 exerts a bactericidal effect on the cells of Staphylococcus aureus Wood 46, which is comparable with the effect of cathelicidin LL-37, as well as pronounced antifungal activity against the clinical isolates of Candida albicans , Cryptococcus neoformans , Rhodotorula mucilaginosa , Trichosporon cutaneum , Geotrichum sp. The MICs of polypeptide SE-33 for different fungal strains were in the range of 31.2 to 1024 μg/mL. Polypeptide SE-33 demonstrated high activity in vivo in the model of vulvovaginal candidiasis (VVC) in mice comparable with that of pimafucin. In the absence of side effects and signs of pathology, polypeptide SE-33 in all doses tested (1, 10 and 50 mg/mL) statistically reduced the vaginal load of the mice compared to the placebo group. The pronounced antibacterial and antifungal activity of polypeptide SE-33, as well as the absence of a toxic effect in the VVC model in mice, suggest polypeptide SE-33 as a promising antimicrobial agent.

The paper presents the results of an open-label, placebo-controlled phase II/III clinical trial of an immunomodulatory drug Polymuramyl in patients with purulent surgical infections. An experimental group of 30 patients received the standard treatment together with Polymuramyl in a dose of 200 mcg IM once daily for 5 days. A control group of 30 patients received the standard treatment only. Polymuramyl significantly accelerated resolution of inflammation, reduced time to normalization of the body temperature, reduced pain, sleep disturbances and general discomfort. The overall effectiveness of treatment was judged as good in 83,3% patients in the Polymuramyl group and only in 56,7% in the control group (p<0,05 in the x-square test). Only one adverse event was registered in the Polymuramyl group, which was not caused by the drug being tested and did not require medical intervention. The laboratory examination revealed that Polymuramyl stimulated the components of the immune system that are involved in the elimination of extracellular purulent bacteria. In conclusion, Polymuramyl can be used as an auxilliary treatment of purulent surgical infection.

Background. The purpose was to investigate a-defensin levels in neutrophiles of pyodermia patients in comparison with healthy donors, to estimate clinical efficiency of glucosaminyl muramyl dipeptide (Licopid) and its influence on a-defensin levels. Materials and method. 31 patients with pyodermia and 17 healthy donors were investigated. Intracellular a-defensin levels in neutrophiles in the peripheral blood were estimated by flow cytometry with mouse anti-NPantibodies (Hy cult biotechnology). All patients with pyodermia were treated with Licopid 10 mg once a day within 10 days. Clinical and laboratory results were measured after 7-0 days course of treatment and one month after treatment. Results. The a-defensin level in patients with pyodermia was reduced in comparison with healthy donors. Immune therapy with licopid 10 mg once a day as a complex treatment lead to a-defensin level increase in leukocytes of peripheral blood. Conclusion. The treatment with licopid 10 mg a day lead to prolonged remission and to increase of endocellular a-defensin level. Definition of a-defensin levels can be useful for advisability and for selection of immune therapy in pyodermia patients. Thus, a decrease of a-defensin levels in pyodermia patients, possibly, is a marker of the chronic bacterial inflammation.

This work was designed to study expression of Toll 1-10 receptors on the surface of cells present in inflammatory infiltrate from nasal polyps and peripheral blood of the patients with polypous rhinosinusitis. It was shown that the intensity of expression depended on the pathomorphological characteristics of nasal polyps. Tissues removed from the patients with polyps of the oedematous type contained more Toll-10 positive cells and showed enhanced expression of Toll-5 receptors on monocytes and lymphocytes, Toll-3 receptors on monocytes, granulocytes, and lymphocytes, and Toll-9 receptors on granulocytes. In contrast, patients with polypous rhinosinusitis and nasal polyps of the fibroedematous type exhibited suppressed expression of Tol-7 receptors on monocytes and Toll-10 receptors on granulocytes coupled to the reduced number of Toll-6 positive lymphocytes as well as enhanced expression of Toll-1 receptors on monocytes, Toll-4 and Toll-5 receptors on granulocytes, and Toll-5 receptors on lymphocytes. It is concluded that only Toll-1, Toll-3, Toll-4, Toll-5, Toll-7, Toll-9 and Toll-10 receptors of their ten types identified thus far in patients with polypous rhinosinusitis and two pathomorphological variants of nasal polyps undergo modulation of expression. These findings open up prospects for the use of new methods for the management of patients with polypous rhinosinusitis by affecting selected components of congenital immunity.

Results of the study on adaptive immunity in patients with polypous rhinosinusitis (PRS) proved to depend on the degree of eosinophilia in the peripheral blood. The patients were allocated to two groups, one comprised of those having up to 150 eosinophils per 1 microliter the other of the patients with a higher eosinophil concentration. Patients of the former group had a significantly reduced number of CD3+, CD4+, CD8+, and CD20+cells in the peripheral blood that may indicate the necessity of administering immunotropic agents. The opposite picture is characteristic of the latter group in which a rise in the number of the above cells is associated with the increased amount of IgG- and IgA-positive cells. In this situation, the use of systemic immunotropic agents should be restricted. It is concluded that evaluation of systemic and local adaptive immunity is of importance for the choice of an adequate strategy for the treatment of patients with polypous rhinosinusitis.

Cathelicidins are a family of cationic amphipathic antimicrobial polypeptides, which play an important role in innate and adaptive immunity. The knowledge of biological effects of these peptides allows to use them not only as an alternative to common antimicrobial therapies. Cathelicidins may also be used for the re-activation of an immune system that has been suppressed by an infection or inflammation, for modulation of inflammation as lipopolysaccharide-binding drugs, and for the activation of regenerative processes. Besides, examination of cathelicidins may serve to detect individuals prone to infectious diseases, to monitor infectious process control in these patients, and to select efficient therapy.

The purpose of research. The purpose was to investigate alpha-defensin levels in the circularly neutrophiles of atopic dermatitis and pyodermia patients in comparison with healthy donors. Materials and methods. 27 patients with atopic dermatitis, 31 patients with pyodermia in comparison with 17 healthy donors were investigated. Intracellular alpha-defensin levels in neutrophils in the peripheral blood were estimated by flow cytometry with mouse anti-HNP-antibodies (Hy cult biotechnology). Results. The alpha-defensins level in patients with atopic dermatitis and pyodermia was reduced in comparison with healthy donors. More expressed decrease of alpha-defensins level was obtained in patients with pyodermia and sever atopic dermatitis with skin infection. Conclusion. Thus, a decrease of alpha-defensins levels in atopic dermatitis and pyodermia patients, possibly, is a marker of the chronic bacterial inflammation and may cause chronic bacterial skin disease, St. aureus colonizations and tolerance to the therapy.

Продукция природных катионных пептидов - важный механизм врожденного иммунитета человека. βДефензины человека принадлежат семейству катионных трисульфидсодержащих микробоцидных пептидов. Кроме прямых антимикробных функций, βдефензины играют множественную роль как ме диаторы воспаления, влияют на хемотаксис, обладают иммуномодулирующей, цитотоксической и др. активностями. Более того, βдефензины рассматриваются как лекарства нового поколения, которые мож но будет использовать как антибактериальные средства, как модуляторы воспаления и при терапии рака. Кроме того, βдефензины играют важную воль в аутоиммунных патологиях