Comparative studies of Toll-like receptor signalling using zebrafish

• Zebrafish larvae are increasingly used for studies of innate immunity.
• We compare the knowledge on TLR signalling in zebrafish and mammals.
• The role of negative control elements in TLR signalling is highlighted.
• There are many advantages of comparative studies of zebrafish and common carp.
• Future studies of TLR signalling will benefit from advances in zebrafish genetics.

Zebrafish model systems for infectious disease are increasingly used for the functional analysis of molecular pattern recognition processes. These studies benefit from the high conservation level of all innate immune factors in vertebrates. Zebrafish studies are strategically well positioned for this because of the ease of comparisons with studies in other fish species of which the immune system also has been intensively studied, but that are currently still less amendable to detailed genetic or microscopic studies. In this paper we focus on Toll-like receptor (TLR) signalling factors, which currently are the best characterized in mammalian systems. We review the knowledge on TLR signalling in the context of recent advances in zebrafish studies and discuss possibilities for future approaches that can complement studies in cell cultures and rodent models. A focus in these comparisons is the role of negative control mechanisms in immune responses that appear very important in a whole organism to keep adverse systemic responses in check. We also pay much attention to comparisons with studies in common carp that is highly related to zebrafish and that because of its large body mass can complement immune studies in zebrafish.