The Rel protein DIF mediates the antifungal but not the antibacterial hostdefense in Drosophila

We have isolated two Drosophila lines that carry point mutations in the gen e coding for the NF-kappa B-like factor DIF. Like mutants of the Toll pathw ay, Dif mutant flies are susceptible to fungal but not to bacterial infecti ons. Genetic epistasis experiments demonstrate that Dif mediates the Toll-d ependent control of the inducibility of the antifungal peptide gene Drosomy cin. Strikingly, DIF alone is required for the antifungal response in adult s, but is redundant in larvae with Dorsal, another Rel family member. In Dr osophila, Dif appears to be dedicated to the antifungal defense elicited by fungi and gram-positive bacteria. We discuss in this light the possibility that NF-kappa B1/p50 might be required more specifically in the innate imm une response against gram-positive bacteria in mammals.