Toll-Like Receptors, Keys of the Innate Immune System

Abstract

Toll-like receptors (TLRs) are members of the integral glycoproteins family, which are consist of intracellular and endoplasmic domains. TLRs are widely distributed in body tissues and expressed by immune and nonimmune cells. They are able to identify pathogens that cause cell injury and distinguish them from harmless microbes, and pathogenic nucleic acids as their binding ligand. Upon binding to their ligands, TLRs first underwent conformational changes; either forming homodimers or heterodimers, starting signaling pathways involve adaptor molecules utilization and then signal transduction through either myeloid differential (MyD)-88 dependent or independent pathways. Ending with activation of several transcription factors (TF) and release of pro-inflammatory cytokines (CK) and Type I interferons (IFN) and initiation of inflammation. TLRs are involved in almost all-inflammatory processes due to underlying disorders and diseases, which made them interesting targets for therapeutic development, via the synthesis of different agonists, antagonists, and even naturalized antibodies.

Differential Production of Midkine and Pleiotrophin by Innate APCs upon Stimulation through Nucleic Acid-Sensing TLRs

“…This is potentially regulated by the various pathways that they might induce and the different factors that can control them in the innate APCs. Human iAPCs express TLRs 1–10 with the exception of pDCs that express TLRs 7 and 9 only [ 42 , 43 ]. The latter express high levels of TLRs 7 and 9, while unstimulated monocytes have high levels of all expressed TLRs except TLR7 [ 44 ].…”