Regulation of immune response by permafrost microorganism metabolites via effector T-lymphocytes

Infectious agents have closely interacted with the human immune system, acquiring a set of highly sophisticated mechanisms for modulating immunity. One of the survival strategies for viruses, bacteria, protozoa, helminths and fungi is to target the regulatory T cell network (Treg: CD4+CD25hiCD127–) that controls immunopathogenic responses in many infections. Not only pathogens but also commensals are able to directly induce the conversion of naive T cells into suppressive Foxp3-expressing Tregs, while others activate pre-existing natural Tregs, in both cases suppressing pathogen-specific effector responses. However, Tregs can also contribute to immunity under certain conditions, such as at the initial stages of infection when effector cells must gain access to the site of infection, and subsequently in ensuring the generation of effector memory cells. It is noteworthy that currently little information on whether infections selectively drive pathogen-specific Tregs, and if so, whether such cells are also reactive to autoantigens are available. Further analysis of Treg subset specificity, along with a clearer picture of relative dynamics during the disease, should lead to rational strategies of immune intervention to optimize immunity and eliminate the infectious process. Thus, restoration of Treg function is important in the treatment of infectious, autoimmune and other diseases and can serve as a marker of their successful treatment. The article assesses the effect of exometabolites of derived from permafrost Bacillus bacteria obtained at different temperature conditions of their cultivation on the activity of Treg and effector T lymphocyte differentiation. Significant differences were established: secondary microbial exometabolites affect Treg (CD4+CD25hiCD127–) differentiation and expression of activation markers (CD69, CD25, HLA-DR) on CD4+ and CD8+ T lymphocytes. This effect is regulated by the type of metabolites obtained at different temperatures — “cold” (obtained at 5°C of bacterial incubation), “medium-temperature” (at 22°C) and “heat” (at 37°C) metabolites. In this case, an increase in the Treg level is associated with lower differentiation activity of CD4+ T-lymphocytes exposed to “cold” secondary exometabolites, a decrease in the differentiation activity of CD8+ T-lymphocytes treated with “warm” secondary exometabolites, and a roughly equivalent effect on the differentiation activity of CD4+ and CD8+ T-lymphocytes acted upon by “medium-temperature” secondary exometabolites.