Annals of the Russian academy of medical sciencesAnnals of the Russian academy of medical sciences0869-60472414-3545"Paediatrician" Publishers LLC117910.15690/vramn1179Research ArticleThe role of lipids in the signaling mechanisms of toll-like receptorsKytikovаO. Yu.<p>MD, PhD</p>kytikova@yandex.ruhttps://orcid.org/0000-0001-5018-0271NovgorodtsevaT. P.<p>PhD in Biology, Professor</p>nauka@niivl.ruhttps://orcid.org/0000-0002-6058-201XDenisenkoYu. K.<p>MD in Biology</p>karaman@inbox.ruhttps://orcid.org/0000-0003-4130-8899AntonyukM. V.<p>MD, PhD, Professor</p>antonyukm@mail.ruhttps://orcid.org/0000-0002-2492-3198GvozdenkoT. A.<p>MD, PhD, Professor</p>vfdnz@mail.ruhttps://orcid.org/0000-0002-6413-9840Far Eastern Scientific Center of Physiology and Pathology of Respiration151220207565855931101202008122020Copyright © 2020, "Paediatrician" Publishers LLC2020<p><em>Toll-like receptors (TLRs) are important players in innate and adaptive immune responses involved in the initiation of the inflammatory process in response to the stimulating influence of endogenous (аllarmine) and exogenous ligands (pathogens viruses, bacteria, fungi). It has now become apparent that not only viral and bacterial infections but non-infectious inflammatory diseases are accompanied by the activation of inflammatory response systems and the development of chronic inflammation associated with disorders in the regulation of the TLRs system. In this regard, the ligand-independent activation of TLRs, which occurs with the participation of lipids, is actively studied. Their signalling functions of TLRs implemented in unique microdomains does membrane lipid rafts that coordinate many cellular processes. The ability to activate TLRs has been found for saturated fatty acids (SFAs), both exogenous and endogenous. On the other hand, TLRs can be inhibited by omega-3 polyunsaturated fatty acids (PUFAs), which can block the inflammatory process. The activation of TLRs triggers a signal cascade that induces the production of reactive oxygen and nitrogen species. The development of oxidative stress is accompanied by the formation of oxidized forms of phospholipids (Ox-PLs), which also induce the development of chronic inflammation. At the same time, Ox-PLs is characterized not only by pro-inflammatory but also anti-inflammatory activity, which necessitates in-depth studies of their role in the implementation of these processes. This review article discusses the mechanisms by which SFAs, PUFAs, and Ox-PLs modulate TLRs activation in lipid rafts. 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