Pathogen Recognition Sem1 Presents Pathogens to Toll

How cells can recognize foreign matter from self is a critical question in immune responses in organisms as diverse as flies and humans. Michel et al. describe a circulating peptidoglycan recognition protein-encoding gene (sem1) in Drosophila that is important for mediating Toll receptor-mediated responses to Gram-positive bacteria, but apparently is not involved in Toll-mediated responses to fungal infection. Genetic analysis suggested that sem1 is upstream of the Toll receptor, consistent with its putative location in Drosophila hemolymph (injection of wild-type hemolymph into sem1 mutant flies restored expression of the antimicrobial peptide drosomycin in response to Gram-positive bacteria). Kaisho and Akira discuss the similarities and differences in Toll and Toll-like receptor-mediated immune responses in mammals and flies. For a more comprehensive analysis of Toll-like receptors, see O'Neill.

T. Michel, J.-M. Reichhart, J. A. Hoffmann, J. Royet, Drosophila Toll is activated by Gram-positive bacteria through a circulating peptidoglycan recognition protein. Nature 414, 756-759 (2001). [Online Journal]

T. Kaisho, S. Akira, Immunology: Bug detectors. Nature 414, 701-703 (2001). [Online Journal]

L. A. J. O'Neill, The interleukin-1 receptor/Toll-like receptor superfamily: Signal transduction during inflammation and host defense. Science's STKE (2000), http://www.stke.org/cgi/content/full/OC_sigtrans;2000/44/re1. [Abstract] [Full Text]