In Drosophila, the Toll signaling pathway regulates the antifungal host defense. In this immune response, when the ligand Spaetzle (Spz) binds to the Toll receptor, the antimicrobial peptide drosomycin is up-regulated. Levashina et al. now add Spn43Ac, a member of the serpin family of serine protease inhibitors, to the Toll cascade. When Spn43Ac is eliminated, Spz is continuously cleaved, which leads to the constitutive activation of Toll signaling; Spn43Ac negatively regulates Toll. In bacterial infection, the lipopolysaccharide (LPS) component of the Gram-negative bacterial cell wall is sensed by the host cells, which triggers an immune response involving the Toll pathway. Toll has been reported to act as a pattern recognition receptor in mammals for LPS. Because the Spn43Ac is located upstream of Toll in Drosophila, Toll does not appear to be its pattern recognition signal. The actual pattern recognition signal in Drosophila is still unknown.
Levashina, E.A., Langley, E., Green, C., Gubb, D., Ashburner, M., Hoffman, J.A., Reichart, J-M. (1999) Constitutive activation of Toll-mediated antifungal defense in serpin-deficient Drosophila. Science 285: 1917-1919. [Abstract] [Full Text]