Dynamics of immunological and microbiological indicators of oral fluid in caries therapy

2022

Microorganisms

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Metabolites and fragments of bacterial cells play an important role in the formation of immune homeostasis. Formed in the course of evolution, symbiotic relationships between microorganisms and a macroorganism are manifested, in particular, in the regulation of numerous physiological functions of the human body by the innate immunity receptors. Low molecular weight bioregulators of bacterial origin have recently attracted more and more attention as drugs in the prevention and composition of complex therapy for a wide range of diseases of bacterial and viral etiology. Signaling networks show cascades of causal relationships of deterministic phenomena that support the homeostasis of multicellular organisms at different levels. To create networks, data from numerous biomedical and clinical research databases were used to prepare expert systems for use in pharmacological and biomedical research with an emphasis on muramyl dipeptides. Muramyl peptides are the fragments of the cell wall of Gram-positive and Gram-negative bacteria. Binding of muramyl peptides with intracellular NOD2 receptors is crucial for an immune response on pathogens. Depending on the microenvironment and duration of action, muramyl peptides possess positive or negative regulation of inflammation. Other factors, such as genetic, pollutions, method of application and stress also contribute and should be taken into account. A system biology approach should be used in order to systemize all experimental data for rigorous analysis, with the aim of understanding intrinsic pathways of homeostasis, in order to define precise medicine therapy and drug design.

Section: Effect Of Muramyl Peptides On Microorganismsmentioning

confidence: 96%

Section: Effect Of Muramyl Peptides On Microorganismsmentioning

confidence: 99%

Regulation of Immune Homeostasis via Muramyl Peptides-Low Molecular Weight Bioregulators of Bacterial Origin

2022

Microorganisms

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“…The absence of defensin expression contributes to an increase in the number of pathogenic bacteria and is observed in inflammatory bowel diseases [ 206 ]. At the same time, an increased amount of defensins may indicate the intensity of the immune response when the content of opportunistic pathogens is increased [ 207 ].…”

Section: Immunomodulatory Activity Of Ampsmentioning

confidence: 99%

Immunomodulatory and Allergenic Properties of Antimicrobial Peptides

Ovchinnikova

2022

IJMS

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With the growing problem of the emergence of antibiotic-resistant bacteria, the search for alternative ways to combat bacterial infections is extremely urgent. While analyzing the effect of antimicrobial peptides (AMPs) on immunocompetent cells, their effect on all parts of the immune system, and on humoral and cellular immunity, is revealed. AMPs have direct effects on neutrophils, monocytes, dendritic cells, T-lymphocytes, and mast cells, participating in innate immunity. They act on B-lymphocytes indirectly, enhancing the induction of antigen-specific immunity, which ultimately leads to the activation of adaptive immunity. The adjuvant activity of AMPs in relation to bacterial and viral antigens was the reason for their inclusion in vaccines and made it possible to formulate the concept of a “defensin vaccine” as an innovative basis for constructing vaccines. The immunomodulatory function of AMPs involves their influence on cells in the nearest microenvironment, recruitment and activation of other cells, supporting the response to pathogenic microorganisms and completing the inflammatory process, thus exhibiting a systemic effect. For the successful use of AMPs in medical practice, it is necessary to study their immunomodulatory activity in detail, taking into account their pleiotropy. The degree of maturity of the immune system and microenvironment can contribute to the prevention of complications and increase the effectiveness of therapy, since AMPs can suppress inflammation in some circumstances, but aggravate the response and damage of organism in others. It should also be taken into account that the real functions of one or another AMP depend on the types of total regulatory effects on the target cell, and not only on properties of an individual peptide. A wide spectrum of biological activity, including direct effects on pathogens, inactivation of bacterial toxins and influence on immunocompetent cells, has attracted the attention of researchers, however, the cytostatic activity of AMPs against normal cells, as well as their allergenic properties and low stability to host proteases, are serious limitations for the medical use of AMPs. In this connection, the tasks of searching for compounds that selectively affect the target and development of an appropriate method of application become critically important. The scope of this review is to summarize the current concepts and newest advances in research of the immunomodulatory activity of natural and synthetic AMPs, and to examine the prospects and limitations of their medical use.

“…The microbiome contributes to the formation and maturation of the immune system and the formation of homeostatic relationships, supporting innate and adaptive immunity [5]. In turn, the host's organism affects microorganisms, regulating the production of immunoglobulin IgA; antimicrobial components, such as defensins; and providing tolerance, thus contributing to the preservation of commensal microflora on the mucosal surface [6][7][8].…”

Section: Introductionmentioning

confidence: 99%

“…In the case of impaired functions of the cells of the pulmonary epithelium, for example, damage to the cilia of the mucous membrane or an excessive amount of secreted mucus, observed during allergic processes, colonization by microorganisms occurs, which can lead to infectious pathologies [9]. Systemic inflammation or inhibition of the phagocytic activity of macrophages can also cause changes in the lung microbiome [3][4][5]8].…”

Section: Introductionmentioning

confidence: 99%

Dual Effect of Low-Molecular-Weight Bioregulators of Bacterial Origin in Experimental Model of Asthma

Гигани

Gudima

et al. 2022

Life

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Asthma is one of the most common noncommunicable diseases, affecting over 200 million people. A large number of drugs control asthma attacks, but there is no effective therapy. Identification of reasons for asthma and preventing this disease is a relevant task. The influence of bacterial components is necessary for the normal development of the immune system and the formation of an adequate immune response to antigens. In the absence of microorganisms or their insufficient exposure, the prerequisites are formed for excessive reactivity to harmless antigens. In the present study, we analyzed cellular and humoral factors in a standard mouse model of OVA-induced asthma modified by 5-fold intraperitoneal injection of bacterial cell wall fragments of glucosaminylmuramyl dipeptide (GMDP) 5 μg/animal or 1 μg lipopolysaccharide (LPS) per animal for 5 days before sensitization by ovalbumin (OVA). Preliminary administration of LPS or GMDP to animals significantly reduced goblet cells as well as the number of neutrophils, lymphocytes, and eosinophils in bronchoalveolar lavage, wherein GMDP corrected neutrophilia to a 2-fold degree, and LPS reduced the severity of eosinophilia by 1.9 times. With OVA administration of GMDP or LPS at the sensitization stage, an increase in the total number of bronchoalveolar lavage cells due to neutrophils, macrophages, lymphocytes, and eosinophils in relation to the group with asthma without GMDP or LPS was observed. The administration of GMDP or LPS to normal mice without asthma for 5 days had no statistically significant effect on the change in the number and population composition of cells in bronchoalveolar lavage in comparison with the control group receiving PBS. As a result of a study in a mouse model of asthma, a dual effect of LPS and GMDP was established: the introduction of LPS or GMDP before sensitization reduces neutrophilia and eosinophilia, while the introduction of LPS or GMDP together with an allergen significantly increases neutrophilia and eosinophilia. The study of the immunoglobulin status shows that in normal-asthma mice, GMDP and LPS slightly increase IgA in bronchoalveolar lavage; at the same time, in the asthma model, injections of GMDP or LPS before sensitization contribute to a significant decrease in IgA (2.6 times and 2.1 times, respectively) in BALF and IgE (2.2 times and 2.0 times, respectively) in blood serum. In an experimental model of asthma, the effect of GMDP and LPS was multidirectional: when they are repeatedly administered before sensitization, the bacterial components significantly reduce the severity of the allergic process, while in the case of a joint injection with an allergen, they increase the influx of macrophages, lymphocytes, and neutrophils into the lungs, which can aggravate the course of pathological process. Thus, the insufficient effect of antigens of a bacterial nature, in particular, with prolonged use of antibiotics can be compensated for by substances based on low-molecular-weight bioregulators of bacterial origin to establish the missing signals for innate immunity receptors, whose constant activation at a certain level is necessary to maintain homeostasis.