Toll-Like Receptors: Linking Innate and Adaptive Immunity

Abstract

Work in recent years has shown an essential role for Toll-like receptors (TLRs) in the activation of innate and adaptive immunity in vertebrate animals. These germ-line encoded receptors, expressed on a diverse variety of cells and tissues, recognize conserved molecular products derived from various classes of pathogens, including Gram-positive and -negative bacteria, DNA and RNA viruses, fungi and protozoa. Ligand recognition induces a conserved host defense program, which includes production of inflammatory cytokines, upregulation of costimulatory molecules, and induction of antimicrobial defenses. Importantly, activation of dendritic cells by TLR ligands is necessary for their maturation and consequent ability to initiate adaptive immune responses. How responses are tailored by individual TLRs to contain specific classes of pathogens is not yet clear.

Mannan-binding lectin directly interacts with Toll-like receptor 4 and suppresses lipopolysaccharide-induced inflammatory cytokine secretion from THP-1 cells

“…The secreted inflammatory cytokines then stimulate macrophages and natural killer cells that can directly kill pathogens or control the initiation of adaptive responses. 19 Lipopolysaccharide (LPS), the major constituent of the outer membrane of Gram-negative bacteria and a strong activator of the inflammatory response and immune regulation, can activate human monocytes and induce them to secrete TNF-a and IL-12. 20 Among the TLR family, TLR4 is expressed very extensively (e.g., monocytes, macrophages, immature DCs, T cells and B cells) and plays a critical role in recognition and signaling of bacterial LPS.…”

Polymorphisms in Toll-like receptor genes and risk of cancer

“…TLR4, the lipopolysaccharide (LPS) receptor, was initially identified as the potential signalling receptor for H. pylori on gastric epithelial cells (Su et al, 2003). TLR4 belongs to a family of pattern recognition receptors, of which there are currently 11 members, that activate pro-inflammatory signalling pathways in response to microbes or pathogen-associated molecular patterns (Pasare and Medzhitov, 2005). TLR4, in conjunction with CD14 and MD-2, transduces signals through MyD88, Toll/IL-1 receptor domain and TRAF6.…”

“…TLRs have the ability to recognize pathogens or pathogen-derived products and initiate signalling events leading to activation of innate host defences (Pasare and Medzhitov, 2005). Signalling by TLRs induces antimicrobial genes and pro-inflammatory cytokines and chemokines and leads to acute inflammatory responses (Janeway and Medzhitov, 2002).…”

Staphylococcus aureus lipoproteins trigger human corneal epithelial innate response through toll-like receptor-2

“…These receptors recognize the highly conserved structural motifs called pathogen-associated molecular patterns (PAMPs) [9]. At least 11 TLRs and their distinct ligands have been identified so far in mammals [12]. Among these receptors, TLR2 is activated by several bacterial products, including lipoproteins, peptidoglycan (PGN), and lipoteichoic acids (LTA), presumably in combination with TLR1 or TLR6 [9].…”