Microbe‐inducible trafficking pathways that control Toll‐like receptor signaling

The receptors of the mammalian innate immune system are designed for rapid microbial detection, and are located in organelles that are conducive to serve these needs. However, emerging evidence indicates that the sites of microbial detection are not the sites of innate immune signal transduction. Rather, microbial detection triggers the movement of receptors to regions of the cell where factors called sorting adaptors detect active receptors and promote downstream inflammatory responses. These findings highlight the critical role that membrane trafficking pathways play in the initiation of innate immunity to infection. In this review, we describe pathways that promote the microbe‐inducible endocytosis of Toll‐like receptors (TLRs), and the microbe‐inducible movement of TLRs between intracellular compartments. We highlight a new class of proteins called Transporters Associated with the eXecution of Inflammation (TAXI), which have the unique ability to transport TLRs and their microbial ligands to signaling‐competent regions of the cell, and we discuss the means by which the subcellular sites of signal transduction are defined.