Gram-negative bacteria-binding protein, a pattern recognition receptor forlipopolysaccharide and beta-1,3-glucan that mediates the signaling for theinduction of innate immune genes in drosophila melanogaster cells

Pattern recognition receptors, non-clonal immune proteins recognizing commo n microbial components, are critical for non-self recognition and the subse quent induction of Rel/NF-kappaB-controlled innate immune genes. However, t he molecular identities of such receptors are still obscure. Here, we prese nt data showing that Drosophila possesses at least three cDNAs encoding mem bers of the Gram-negative bacteria-binding protein (DGNBP) family, one of w hich, DGNBP-1, has been characterized, Western blot, flow cytometric, and c onfocal laser microscopic analyses demonstrate that DGNSP-1 exists in both a soluble and a glycosylphosphatidylinositol-anchored membrane form in cult ure medium supernatant and on Drosophila immunocompetent cells, respectivel y. DGNBP-1 has a high affinity to microbial immune elicitors such as lipopo lysaccharide (LPS) and beta -1,3-glucan whereas no binding affinity is dete cted with peptidoglycan, beta -1,4-glucan, or chitin, Importantly, the over expression of DGNBP-1 in Drosophila immunocompetent cells enhances LPS- and beta -1,5-glucan-induced innate immune gene (NF-kappaB-dependent antimicro bial peptide gene) expression, which can be specifically blocked by pretrea tment with anti-DGNBP-1 antibody, These results suggest that DGNBP-1 functi ons as a pattern recognition receptor for LPS from Gram-negative bacteria a nd beta -1,3-glucan from fungi and plays an important role in non-self reco gnition and the subsequent immune signal transmission for the induction of antimicrobial peptide genes in the Drosophila innate immune system.