Toll-like receptor signaling pathway

Toll-like receptors (TLRs) are membrane-bound receptors identified as homologs of Toll in Drosophila and are responsible for detecting microbial pathogens and generating innate immune responses. The Toll-like Receptors of pattern recognition receptors detects a wide range of viruses, bacteria, fungi, and parasites via pathogen-associated molecular patterns (PAMPs). These PAMPs include cell wall components such as endotoxin, as well as pathogenic DNA and RNA. Mammalian TLRs are expressed on innate immune cells, such as macrophages and dendritic cells, and respond to the membrane components of Gram-positive or Gram-negative bacteria. Pathogen recognition by TLRs provokes rapid activation of innate immunity by inducing production of pro-inflammatory cytokines and up-regulation of co-stimulatory molecules. Decade years ago, emerging evidence revealed that all TLRs activate MyD88-dependent pathways to induce a core set of stereotyped responses, such as inflammation. Each receptor binds to specific ligands, initiates a tailored innate immune response to the specific class of pathogen, and activates the adaptive immune response. With deep research, TLR signaling pathways are separated into two groups now: a MyD88-dependent pathway that leads to the production of pro-inflammatory cytokines with quick activation of NF-{kappa}B and MAPK, and a MyD88-independent pathway associated with the induction of IFN-beta and IFN-inducible genes, and maturation of dendritic cells with slow activation of NF-{kappa}B and MAPK.


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