Negative regulation of toll-like receptor-mediated immune responses

Nat Rev Immunol. 2005 Jun;5(6):446-58. doi: 10.1038/nri1630.


Toll-like receptors (TLRs) are involved in host defence against invading pathogens, functioning as primary sensors of microbial products and activating signalling pathways that induce the expression of immune and pro-inflammatory genes. However, TLRs have also been implicated in several immune-mediated and inflammatory diseases. As the immune system needs to constantly strike a balance between activation and inhibition to avoid detrimental and inappropriate inflammatory responses, TLR signalling must be tightly regulated. Here, we discuss the various negative regulatory mechanisms that have evolved to attenuate TLR signalling to maintain this immunological balance.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Apoptosis / immunology
  • Communicable Diseases / immunology
  • Down-Regulation / immunology
  • Humans
  • Immunity, Innate
  • Interleukin-1 Receptor-Associated Kinases
  • Intracellular Signaling Peptides and Proteins / immunology
  • Membrane Glycoproteins / biosynthesis
  • Membrane Glycoproteins / chemistry
  • Membrane Glycoproteins / immunology*
  • Phosphatidylinositol 3-Kinases / immunology
  • Protein Kinases / immunology
  • Receptors, Cell Surface / biosynthesis
  • Receptors, Cell Surface / chemistry
  • Receptors, Cell Surface / immunology*
  • Receptors, Interleukin-1 / immunology
  • Repressor Proteins / immunology
  • Signal Transduction / immunology
  • Suppressor of Cytokine Signaling 1 Protein
  • Suppressor of Cytokine Signaling Proteins
  • Toll-Like Receptors


  • Intracellular Signaling Peptides and Proteins
  • Membrane Glycoproteins
  • Receptors, Cell Surface
  • Receptors, Interleukin-1
  • Repressor Proteins
  • SOCS1 protein, human
  • Suppressor of Cytokine Signaling 1 Protein
  • Suppressor of Cytokine Signaling Proteins
  • Tir8 protein, mouse
  • Toll-Like Receptors
  • Protein Kinases
  • Phosphatidylinositol 3-Kinases
  • Interleukin-1 Receptor-Associated Kinases