TLR cross-talk confers specificity to innate immunity

Int Rev Immunol. 2014 Nov-Dec;33(6):443-53. doi: 10.3109/08830185.2014.921164. Epub 2014 Jun 9.


Cross-talk within the innate immune pathways is highly complex and contains many unknowns. Here, we discuss the different combinations of PAMPs, together with the sequence, order, and dosage of consecutive PAMP challenges, which determine the nature of the immune response by macrophages. The engagement of different Toll-like receptor (TLR) ligands leads to quantitatively and qualitatively unique cytokine production, showing that TLR pathway crosstalk enables the innate immune system to orchestrate immediate local and global responses. It is likely that multiple pathways are involved in the regulation of cytokine synergy, including many that have yet to be discovered.

Keywords: cytokines; macrophage; pathogen recognition; signaling cross-talk; toll-like receptors.

Publication types

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

MeSH terms

  • Animals
  • Cytokines / metabolism
  • Humans
  • Immunity, Innate
  • Ligands
  • Macrophages / immunology*
  • Receptor Cross-Talk
  • Signal Transduction*
  • Toll-Like Receptors / agonists*


  • Cytokines
  • Ligands
  • Toll-Like Receptors