Mechanisms of Toll-like receptor tolerance induced by microbial ligands

Abstract

Some microorganisms can develop tolerance. On the one hand, it allows pathogenic microbes to escape immune surveillance, on the other hand, it provides the possibility to microbiota representatives to colonize different biotopes and build a symbiotic relationship with the host. Complex regulatory interactions between innate and adaptive immune systems as well as stimulation by antigens help microbes control and maintain immunological tolerance. An important role in this process belongs to innate immune cells, which recognize microbial components through pattern-recognition receptors. Toll-like receptors (TLRs) represent the main class of these receptors. Despite the universality of the activated signaling pathways, different cellular responses are induced by interaction of TLRs with microbiota representatives and pathogenic microbes, and they vary during acute and chronic infection. The research on mechanisms underlying the development of TLR tolerance is significant, as the above receptors are involved in a wide range of infectious and noninfectious diseases; they also play an important role in development of allergic diseases, autoimmune diseases, and cancers. The knowledge of TLR tolerance mechanisms can be critically important for development of TLR ligand-based therapeutic agents for treatment and prevention of multiple diseases.