Pathogen Recognition and Innate Immunity

These findings demonstrate that TLR2 plays a critical role in the innate immune response to M. leprae

Shizuo Akira

2006

Scholarcy highlights

  • Vertebrates are constantly threatened by the invasion of microorganisms and have evolved systems of immune defense to eliminate infective pathogens in the body
  • Microorganisms that invade a vertebrate host are initially recognized by the innate immune system through germline-encoded pattern-recognition receptors
  • Exposure of immune cells to the ligands of these receptors activates intracellular signaling cascades that rapidly induce the expression of a variety of overlapping and unique genes involved in the inflammatory and immune responses
  • New insights into innate immunity are changing the way we think about pathogenesis and the treatment of infectious diseases, allergy, and autoimmunity
  • Viral DNA Is Recognized by TLR9 DNA viruses, including herpes simplex virus 1, HSV-2, and murine cytomegalovirus, contain genomes that are rich in CpG-DNA motifs, and they activate inflammatory cytokines and type I IFN secretion by stimulation of TLR9
  • A complex comprised of myeloid differentiation factor 88, IL-1R-associated kinase 4, IRAK-1, TNFR-associated factor 6, and IRF-7 is formed and recruited to the TLR. plasmacytoid DCs lacking MyD88 or IRAK-4 failed to produce either inflammatory cytokines or IFN-a in response to CpG-DNA stimulation
  • Dissection of the functions of the various TLRs and their signaling pathways has revealed that mammalian innate immune cells activate distinct signaling pathways depending on the pathogen involved in the infection and mount adaptive cytokine responses for each

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