2Russian Medical Academy of Postgraduate Education, Department of Immunology, 123995 Moscow, Russia; E-mail: email@example.com
3Committee on Science and High Technologies, State Duma of the Federal Assembly of Russian Federation, 103265 Moscow, Russia; E-mail: firstname.lastname@example.org
* To whom correspondence should be addressed.
Received November 20, 2014
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-β) 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-β 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.
KEY WORDS: Treg, CD4+CD25highFoxp3+, antigen-presenting cells, IL-10, CTLA-4, immunosuppression, immune evasion