Defining the subcellular sites of innate immune signal transduction

Trends Immunol. 2012 Sep;33(9):442-8. doi: 10.1016/ Epub 2012 Jul 18.


Innate immune activation by microbial detection receptors is a complex process involving at least 100 proteins and multiple signaling pathways. Although there continues to be a need to identify additional regulators of host-microbe interactions, a larger conceptual challenge is our lack of understanding of how the known regulators interact in space and time. This review offers a framework to explain the long appreciated (but poorly understood) observation that innate immune signaling pathways are activated from multiple organelles. Using the Toll-like receptors (TLRs) and the retinoic acid-inducible gene 1 protein (RIG-I)-like receptors (RLRs) as examples, I propose that the receptors do not necessarily define the sites of signaling. Rather, a structurally unrelated class of proteins called 'sorting adaptors' functions in this capacity.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Humans
  • Immunity, Innate*
  • Intracellular Space / immunology*
  • Intracellular Space / metabolism
  • Ligands
  • Receptors, Antigen, T-Cell / immunology
  • Signal Transduction*


  • Ligands
  • Receptors, Antigen, T-Cell