Toll-like receptors: Significance, ligands, signaling pathways, and functions in mammals

Abstract

This review attempts to cover the implication of the toll-like receptors (TLRs) in controlling immune functions with emphasis on their significance, function, regulation and expression patterns. The tripartite TLRs are type I integral transmembrane receptors that are involved in recognition and conveying of pathogens to the immune system. These paralogs are located on cell surfaces or within endosomes. The TLRs are found to be functionally involved in the recognition of self and non-self-antigens, maturation of DCs and initiation of antigen-specific adaptive immune responses as they bridge the innate and adaptive immunity. Interestingly, they also have a significant role in immunotherapy and vaccination. Signals generated by TLRs are transduced through NFκB signaling and MAP kinases pathway to recruit pro-inflammatory cytokines and co-stimulatory molecules, which promote inflammatory responses. The excess production of these cytokines leads to grave systemic disorders like tumor growth and autoimmune disorders. Hence, regulation of the TLR signaling pathway is necessary to keep the host system safe. Many molecules like LPS, SOCS1, IRAK1, NFκB, and TRAF3 are involved in modulating the TLR pathways to induce appropriate response. Though quantification of these TLRs helps in correlating the magnitude of immune response exhibited by the animal, there are several internal, external, genetic and animal factors that affect their expression patterns. So it can be concluded that any identification based on those expression profiles may lead to improper diagnosis during certain conditions.

Toll-like receptors in immunity and inflammatory diseases: Past, present, and future

“…DNAs and RNAs) [79]. However, it is beyond the scope of the present article to discuss the detail of each TLR signaling pathway that is described elsewhere [80][81][82][83][84][85]. Table 1 is summarizing the numbers of TLRs found in mammalian species mainly in humans and laboratory mouse and their role in pathogen recognition, TLR SNPs and disease association and expression pattern.…”

Melatonin, a toll‐like receptor inhibitor: Current status and future perspectives

“…Alternatively, it also activates NF-κB by interacting with receptor-interacting protein-1. TRIF further interacts with TRAF3 and the phosphatidylinositol 3-kinase (PI3K)-AKT pathway resulting in the nuclear translocation of interferon regulatory factor 3 (IRF3) and IRF2, respectively (Brown, Wang, Hajishengallis, & Martin, 2011;Ostuni, Zanoni, & Granucci, 2010;Patel et al, 2012;Vidya et al, 2018).…”

Immunomodulatory activity of Ganoderma lucidum immunomodulatory protein via PI3K/Akt and MAPK signaling pathways in macrophage RAW264.7 cells

“…Our results indicated that the macrophage activation induced by rFIP-glu involved Toll-like receptors and MAPKs signaling pathways in macrophage RAW264.7 cells, which is consistent with that PI3K/Akt, the downstream of Toll-like receptor, and MAPK are involved in the activation of macrophages (34, 87–89). TLR4 is critical in immune responses and involved mainly in inflammation responses (90). TLR4 can be recognized and activated by many stimuli such as polysaccharides, and its expression increases, and then activates PI3K/Akt and MAPKs pathways, with introduction of a pool of inflammatory mediators (30, 34, 43, 87, 91).…”