Inactivation of Inflammasomes by Pathogens Regulates Inflammation.

Inflammatory response is initiated and sustained by the action of quintessential pro-inflammatory cytokines of immune system namely IL-1ß and IL-18. The maturation process of those cytokines is ensured by caspase-1 enzymatic activity, that is in turn is tightly controlled by multiprotein complexes called inflammasomes. Inflammasomes are activated in cells of innate immune system in response to recognition of conservative parts of microbes (pathogen-associated molecular patterns) or by sensing molecular signs of tissue damage (damage-associated molecular patterns). Inflammasome activation apart of cytokines secretion leads to pro-inflammatory cell death, so-called pyroptosis. That culminates in release of cytoplasmatic content of cells including cytokines and alarmins that boost immune response against pathogens, as well as pyroptosis destroys replicative niches of intracellular pathogens. During co-evolution with the host, bacterial and viral pathogens developed a range of molecular inhibitors targeting each step of inflammasome activation. In current review, we will discuss the latest knowledge of inflammasomes' signaling pathways and tricks that pathogens use to avoid immune recognition and clearance. Our better understanding of inflammasome inhibition by pathogens can lead to better therapeutic approaches for the treatment of infectious diseases.

T-Regulatory Cells as Part of Strategy of Immune Evasion by Pathogens.

Under physiological conditions, regulatory processes can suppress the immune response after elimination of a pathogen and restore homeostasis through the destruction and suppression of obsolete effector cells of the immune system. The main players in this process are T-regulatory cells (Tregs) and immature dendritic cells, which suppress the immune response by their own products and/or by inducing synthesis of immunosuppressive interleukins IL-10, IL-35, and transforming growth factor (TGF-ß) by other cells. This mechanism is also used by widespread "successful" pathogens that are capable of chronically persisting in the human body - herpes virus, hepatitis viruses, human immunodeficiency virus, Mycobacterium tuberculosis, Helicobacter pylori, and others. During coevolution of microbial pathogens and the host immune system, the pathogens developed sophisticated strategies for evading the host defense, so-called immune evasion. In particular, molecular structures of pathogens during the interaction with dendritic cells via activating and inhibitory receptors can change intracellular signal transduction, resulting in block of maturation of dendritic cells. Immature dendritic cells become tolerogenic and cause differentiation of Tregs from the conventional T-cell CD4+. Microbial molecules can also react directly with Tregs through innate immune receptors. Costimulation of Toll-like receptor 5 (TLR5) by flagellin increases the expression of the transcription factor Foxp3, which increases the suppressive activity of Treg cells. From all evasion mechanisms, the induction of immunosuppression by Treg through IL-10, IL-35, and TGF-ß appears most effective. This results in the suppression of inflammation and of adaptive immune responses against pathogens, optimizing the conditions for the survival of bacteria and viruses.

[Immune status and proinflammatury cytokines in pregnant women with acute cytomegalovirus infection]. / Immunnyi status i protivovospalitel'nye tsitotoksiny u beremennykh s ostroi tsitomegalovirusnoi infektsiei.

A total of 64 pregnant women aged 16-40 years with acute cytomegalovirus (CMV) infection were examined. CMV infection was diagnosed by the detection of anti- CMV IgM (by the enzyme immunoassay) or DNA by PCR in the blood. The immunophenotype of lymphocytes CD3+, CD4+, CD8+, CD16+, CD19+, IgG, IgM, IgA and the spontaneous production of TNFalpha and IL-8 in the blood were studied. In pregnant women with CMV infection the presence of the immunosuppression of cell-mediated immunity reactions, the hyperproduction of Fc-receptors of natural killers, B lymphocytes (CD19+), the hyperglobulinemia of serum IgM and IgG, as well as the increased synthesis of proinflammatory cytokines--TNFalpha and IL-8--were established.

[Effect of gravitational tidal changes on the periodicity of T-lymphocyte receptor expression in vitro]. / Vliianie prilivnykh izmenenii sily tiazhesti na periodichnost' ékspressii retseptorov T-limfotsitov in vitro.

The hourly registration of the expression of the human s T-lymphocytes subpopulations receptors in vitro during 6 hours demonstrated the existence of the periodicity from 2 to 4 hours. There is high degree of T-lymphocytes expressions coincidence from different individuals depending of the date. For most of daily average individual chronograms, there were described back linear and valid correlations with a character of heterogeneity of the gravity force changes. The results are in according to suggestion about the time field geometric effect to structural-functional cells periodicity.