TLR-mediated innate immune recognition

Abstract

Immune recognition has always been one of the main points of interest in immunology. It is well appreciated that there are several distinct strategies of immune recognition that operate in the mammalian immune system. These are traditionally grouped as innate and adaptive, based on the use of either germline-encoded or somatically-generated receptors, respectively. Beyond the genetic nature of the receptors involved, however, the distinction between the two types of immune recognition is not always clear-cut. For example, complement receptors, TLRs, and presumably other types of non-clonal "innate" immune receptors can cooperate with B cell receptors in pathogen recognition, and this involves, at least in some cases, co-recognition by the two types of receptors. In addition, the architecture of antigen receptor complexes bears a striking resemblance to a class of innate immune receptor complexes that signal through ITAM-containing adaptor proteins, such as DAP12. In both cases multi-protein receptor complexes are assembled through ionic interactions between charged residues in the transmembrane regions and signal through similar pathways involving ITAM dependent activation of Syk-72 and ZAP-70.Although the classification of immune recognition into innate and adaptive is useful in many ways, it may obscure the heterogeneity of receptors and mechanisms of innate immune recognition. Indeed, the mammalian innate immune system uses several different classes of receptors, including TLRs, NODs, and NALPS, Dectins, RIG-I and MDA-5 and others [1,2]. Some of the receptors are transmembrane proteins (e.g., TLRs and Dectins), some are secreted (e.g., penthaxins and collectins), and some are intracellular cytoplasmic receptors (e.g., RIG-I/MDA-5, NODs).

Novel Latency Reversal Agents for HIV-1 Cure

“…Pathogen infections are primarily sensed by the innate immune system through the interaction of conserved molecular structures named pathogen-associated molecular patterns (PAMPs) with host-encoded pattern recognition receptors (PRRs) (72; 73). PRRs are germline-encoded receptors that recognize several classes of molecules typical of pathogens, such as proteins, lipids, carbohydrates and nuclei acids (73).…”

Activation of BV2 microglia by lipopolysaccharide triggers an inflammatory reaction in PC12 cell apoptosis through a toll-like receptor 4-dependent pathway

“…Toll-like receptors (TLRs), which are widely expressed in microglia, could recognize pathogen-associated molecular patterns (PAMP) on the surface of pathogens and initiate intracellular signals that regulate gene expression Medzhitov 2001Medzhitov , 2007Miyake 2007;Rajagopal 2008;Mogensen 2009;Takeuchi and Akira 2010). TLRs are involve in a variety of CNS diseases such as infection, trauma (Arslan et al 2010;Brea et al 2010), neurodegenerative diseases (Ding et al 2011;Kawai and Akira 2006;Panaro et al 2008;Vollmar et al 2009), and autoimmunity.…”

Toll-Like Receptor Polymorphisms, Inflammatory and Infectious Diseases, Allergies, and Cancer

“…MAPKs activate transcription factors activator protein-1 and activating transcription factor 2, leading to their nuclear translocation, binding to promoter regions of target genes, and transcription of inflammatory mediators (Vogel and others 2003;Doyle and O'Neill 2006;Medzhitov 2007;O'Neill 2008;Kawai and Akira 2011). TLR7 and TLR9 activate type I IFNs via the MyD88-IRAK4-IRAK1 signaling module, which then interacts with TRAF6, leading to activation of NF-kB and production of proinflammatory cytokines, or activates TRAF3 and IKK-a, leading to induction of IFN regulatory factor (IRF)-3-and IRF7-dependent type I IFNs, respectively (Fig.…”