A κB sequence code for pathway-specific innate immune responses

The Toll and Imd pathways induce humoral innate immune responses in Drosophila by activating NF-kappa B proteins that bind kappa B target sites. Here, we delineate a kappa B site sequence code that directs pathway-specific expression of innate immune loci. Using bioinformatic analysis of expression and sequence data, we identify shared properties of Imd- and Toll-specific response elements. Employing synthetic kappa B sites in luciferase reporter and in vitro binding assays, we demonstrate that the length of the (G) n element in the 50 half- site and of the central (A, T)-rich region combine to specify responsiveness to one or both pathways. We also show that multiple sites function to enhance the response to either or both pathways. Together, these studies elucidate the mechanism by which kappa B motifs direct binding by particular Drosophila NF-kappa B family members and thereby induce specialized innate immune repertoires.