Evolving function of Toll-like receptor pathways (116.6)

Abstract

The innate and adaptive arms of immunity work synergistically to mount robust host defenses against invading pathogens. The zebrafish lacks a fully functional adaptive immune system for the first four to six weeks of development, making it an ideal model for studying many aspects of innate immunity, including the Toll-like receptor (TLR) pathways. In mammals, TLRs recognize specific pathogen associated molecular patterns and, acting through adaptor molecules such as MYD88 and TICAM1, elicit an array of pro- and anti-inflammatory responses. In two recent studies we described differences in TLR ligand recognition and downstream signaling in the zebrafish, and proved that sequence homology does not necessarily indicate functional homology. These data support the notion that alternative signaling pathways may have evolved in the zebrafish. To characterize this system, ligands of the zebrafish TLRs and the intracellular protein-protein interactions were studied. Here we report the identification of unique interactors and targeted morpholino knock-down of TLR-associated genes to analyze the impact on signaling of each each protein-protein interaction within zebrafish TLR pathways. The discovery of novel protein interactions in the zebrafish highlights the potential of this model system for studies of innate immune function and further elucidates the evolution of vertebrate immunity.