The Role of TLR and RIGI Family Helicases in Viral Infection

TLR Detects Extracellular Pathogen-Associated Molecular Patterns

Toll was first identified as a transmembrane receptor regulating insect morphogenesis (Hashimoto et al. 1988). Toll mutation also results in increased sensitivity to fungi in Drosophila (Lemaitre et al. 1996), leading to the identification of mammalian Toll-like receptors (TLRs) as sensing receptors of various pathogen-associated molecular patterns (PAMPs) (Medzhitov et al. 1997). Ten members of human TLRs are expressed in a tissue-specific manner and many are expressed in dendritic cells (DCs) and macrophages (Takeda and Akira

2005). Although each TLR detects a distinct set of PAMPs, a common extracellular leucine-rich repeat (LRR) motif is responsible for sensing. When LRR

detects a pathogen, a signal is generated in the cytoplasm, which is mediated by the cytoplasmic domain of the receptor. TLR activation results in the production of various cytokines, leading to the activation of innate immune responses (as described in this volume by Severa and Fitzgerald). Upon TLR activation, macrophages and DCs differentiate into antigen-presenting cells initiating antigen-specific acquired immunity. Viral infection is sensed by three TLRs: TLR3 (Alexopoulou et al. 2001), TLR7/8 (Diebold et al. 2004; Heil et al. 2004; Lund et al. 2004), and TLR9 (Hemmi et al. 2000; Krug et al. 2004; Lund et al. 2003), which are mostly expressed on the endosomal membrane (Fig. 1). Double-stranded RNA (dsRNA), single-stranded RNA, and unmethylated CpG DNA are detected by TLR3, TLR7/8, and TLR9, respectively (Fig. 2). This subset of TLRs activates transcription factors including NF-kB, IRF-3, and

PAMPs derived from Nucleic acids pathogens released from infected cells

Tlr Mda5 Rigi

Fig. 1 Recognition of PAMPs by TLR and RIG-I family helicases. Transmembrane receptor TLR is expressed on the plasma or endosomal membranes and senses extracellular PAMPs. RIG-I family helicases detect viral RNA in the cytoplasm. Activation of these receptors transduces signals resulting in overlapping, but in a different set of target genes, including cytokines and chemokines

Fig. 1 Recognition of PAMPs by TLR and RIG-I family helicases. Transmembrane receptor TLR is expressed on the plasma or endosomal membranes and senses extracellular PAMPs. RIG-I family helicases detect viral RNA in the cytoplasm. Activation of these receptors transduces signals resulting in overlapping, but in a different set of target genes, including cytokines and chemokines

PAMPs dsRNA

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ssRNA CpG-DNA

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