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. 2021 Feb 26;12:578386. doi: 10.3389/fimmu.2021.578386

Figure 1.

Figure 1

Main probiotic immune-modulatory pathways in the gut. (A) T cells are considered the masters of inflammation in that they can differentiate into different pathways promoting or suppressing inflammatory response. However, their fate requires interaction with other cells: for instance, dendritic cells. Probiotics can influence these communications through membrane receptors e.g. PRRs. In particular, TLR-6 and TLR-2, a member of PRRs, expressed on sentinel cells such as macrophages and dendritic cells, might be able to decrease the Th17 polarization and skew T-cells toward Treg subpopulation and production of high levels of IL-10 and lower levels of TNF-α, reducing the inflammatory state which could be one of the mechanisms involved in the immune modulatory effect of probiotics in inflammatory intestinal diseases. Probiotics seem to redirect the Th2 response, characteristic of atopic patients, towards a Th1 type through increased secretion of IFN-γ and a decrease in the IL-4, IL-13, and IgE production with improvement of allergic predisposition and reactions. In the gut, probiotics may activate B cells in the lamina propria that become IgA-producing plasma cells. The IgA, a major functional component of the humoral adaptive immune system specialized in mucosal protection and a first line of defense against gastrointestinal infections, is transported across the epithelial cells and once it is secreted in the gut lumen it can bind to the mucus layer covering them. (B) NK cells are intermediate cells between innate and adapted immunity. They seem to act in different ways through an interplay with intestinal epithelial cells, DCs and T cells. Probiotics can modulate their behavior for instance through the secretion of IFN-γ. (C) Finally, probiotics exert their functions by altering intracellular pathways of immune cells (e.g. macrophage) through kinases (such as MAP kinase cascade) which in the end activate or suppress transcription factors: STAT, NF-κB, Jun-1, Fos. On the other hand, probiotics may act on the same pathway through the metabolism of histamine acting on H2-receptors of antigen presenting cells and inducing a reduction of pro-inflammatory cytokines like TNF-α, IL-12 and monocyte chemotactic protein-1.