[Responses with participation of toll-like receptors in protective immunity and in pathologic states]

Toll-like receptors (TLRs) are a group of transmembrane receptors which play a key role in both innate and adaptive immune responses. The specific exogenous ligands of TLRs are pathogen-associated molecular patterns such as peptidoglycan, flagellin, teichoic acid, CPG-containing DNA, and others. Stimulation of TLRs induces synthesis and secretion of cytokines, upregulation of co-stimulatory molecules and functional maturation of antigen-presenting cells and leads to the development of both protective and damaging adaptive immune reactions. TLRs are also able to interact with a number of endogenic ligands such as fibronectine, heat shock proteins and extracellular matrix components. Thus, TLRs are involved in the development of many pathological states including sepsis and aseptic inflammation, allergy and autoimmune diseases, cancer. In the recent years several biotechnology and pharmaceutical companies developed new drugs that are either agonists of TLRs to enhance immune responses against tumours and infecious agents or to correct inadequate immune reactions or antagonists designed to reduce the inflammation caused by infection or autoimmune diseases. The paper presents current data concerning TLRs biology, the contribution of TLRs to pathogenesis of human diseases and completed, ongoing and planned clinical trials with immunotherapeutic drugs based on TLR agonists and antagonists.