Important Aspects of Toll-like Receptors: Signaling Pathways in Diseases
Toll-like receptors (TLRs) are a group of receptors that serve as the body’s first line of defence against microorganisms. They can detect invading pathogens as well as endogenous danger compounds generated by dying cells and damaged tissues, and they serve an important role in bridging the gap between innate and adaptive immunity. TLRs are found in a wide range of immune and non-immune cells. TLR expression and location are altered in response to pathogen-derived or damaged host-cell-derived chemicals. When ligands bind to TLR, they trigger intracellular signalling cascades that launch host defence responses. Recent research has discovered that gastrointestinal epithelial cells express nearly all TLR subtypes known to date, and that TLR expression and activation throughout the GI tract are closely regulated and coordinated. An excessive host defence reaction of the intestinal epithelium to endogenous luminal bacterial flora may be responsible for the initiation and persistence of inflammatory intestinal responses in inflammatory bowel disease (IBD). Several functional Toll-like receptors (TLRs) are expressed constitutively in intestinal epithelial cell lines, and they appear to be essential regulators of the innate response system. Stomach epithelial cells are the first line of defence against H. pylori, and they respond to infection by triggering a series of cell signalling cascades that result in cytokine production and the recruitment of inflammatory cells to the gastric mucosa. Many of these cell signalling processes are mediated by pathogen recognition receptors from the Toll-like receptor (TLR) family. Signaling downstream of toll-like receptors on immunological and resident vascular cells can elicit proinflammatory cytokine release, lipid uptake, and foam cell production, as well as activate cells of the adaptive immune system, which can alter atherogenesis. TLR1, -2, -3, -4, and -6 are expressed by tubular epithelial cells, which suggests that these TLRs may have a role in the activation of immune responses in tubulointerstitial damage (e.g., bacterial pyelonephritis, sepsis, and transplant nephropathy). Several studies have revealed that Toll-like receptors are an important part of our microbial defence system, but their potential involvement as mediators in allergies and asthma has yet to be determined. Toll-like receptor 4, a pathogen-associated molecular pattern receptor that initiates an inflammatory cascade in response to different CNS stimuli, is an essential contributor to microglial activation.
Najah R. Hadi
Professor and Consultant, Faculty of Medicine, University of Kufa, Iraq.
Saad Rasool Shaker
Alzahra Teaching Hospital, Alnajaf Health Directorate, Iraq.
Nada R. Alharis
Professor of Diagnostic Radiology Faculty of Medicine University of Kufa Iraq.