A kappaB sequence code for pathway-specific innate immune responses.
The Toll and Imd pathways induce humoral innate immune responses in Drosophila by activating NF-kappaB proteins that bind kappaB target sites. Here, we delineate a kappaB 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 kappaB sites in luciferase reporter and in vitro binding assays, we demonstrate that the length of the (G)(n) element in the 5' 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 kappaB motifs direct binding by particular Drosophila NF-kappaB family members and thereby induce specialized innate immune repertoires.
Section of Cell and Developmental Biology, University of California at San Diego, La Jolla, CA 92093-0349, USA.
Matthew S
MS
Busse
Christopher P
CP
Arnold
Par
P
Towb
James
J
Katrivesis
Steven A
SA
Wasserman
D000818:Animals; D001483:Base Sequence; D019295:Computational Biology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D004331:Drosophila melanogaster / Q000502:physiology; D017930:Genes, Reporter; D007113:Immunity, Innate; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology; D011485:Protein Binding; D015398:Signal Transduction / Q000502:physiology*; D051193:Toll-Like Receptors / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology
C488990:AttA protein, Drosophila; D004268:DNA-Binding Proteins; C084428:Dif protein, Drosophila; D029721:Drosophila Proteins; D016328:NF-kappa B; C101626:Rel protein, Drosophila; D051193:Toll-Like Receptors; D014157:Transcription Factors; C439909:imd protein, Drosophila