LPS-induced immune response in Drosophila

Abstract

The study of the regulation of the inducible synthesis of antimicrobial peptides in Drosophila melanogaster has established this insect as a powerful model in which to study innate immunity. In particular, the molecular characterization of the regulatory pathway controlling the antifungal peptide drosomycin has revealed the importance of Toll receptors in innate immunity. We report here that injection of LPS into flies induces an immune response, suggesting that LPS receptors are used in Drosophila to detect Gram-negative bacteria infection. We have identified in the recently sequenced genome of Drosophila eight genes coding for Toll-like receptors in addition to Toll, which may function as LPS receptors. However, overexpression of a selection of these genes in tissue-culture cells does not result in up-regulation of the antibacterial peptide genes. These results are discussed in light of the recent data from genetic screens aimed at identifying the genes controlling the antibacterial response in Drosophila.

References

Hoffmann J. , Reichhart J. Drosophila immunity. Trends Cell Biol 1997 ; 7: 309—316.

Ekengren S. , Hultmark D. Drosophila cecropin as an antifungal agent. Insect Biochem Mol Biol 1999; 29: 965—972.

Imler J. , Hoffmann J. Signaling mechanisms in the antimicrobial host defense of Drosophila. Curr Opin Microbiol 2000; 3: 16—22.

Means TK , Golenbock DT , Fenton MJ The biology of Toll-like receptors. Cytokine Growth Factor Rev 2000; 11: 219—232.

Samakovlis C. , Asling B. , Boman H. , Gateff E. , Hultmark D. In vitro induction of cecropin genes: an immune response in a Drosophila blood cell line. Biochem Biophys Res Commun 1992; 188: 1169—1175.

Tauszig S. , Jouanguy E. , Hoffmann J. , Imler J. Toll-related receptors and the control of antimicrobial peptide expression in Drosophila. Proc Natl Acad Sci USA 2000 ; 97: 10520—10525.

Takeuchi O. , Hoshino K. , Kawai T. et al. Differential roles of TLR2 and TLR4 in recognition of Gram-negative and Gram-positive bacterial cell wall components. Immunity 1999; 11: 443—451.

Rock F. , Hardiman G. , Timans J. , Kastelein R. , Bazan J. A family of human receptors structurally related to Drosophila Toll. Proc Natl Acad Sci USA 1998; 95: 588—593.

Luo C. , Zheng L. Independent evolution of Toll and related genes in insects and mammals. Immunogenetics 2000; 51: 92—98.

10.

Gerttula S. , Jin YS , Anderson KV Zygotic expression and activity of the Drosophila Toll gene, a gene required maternally for embryonic dorsal-ventral pattern formation. Genetics 1988; 119: 123—133.

11.

Eldon E. , Kooyer S. , D'Evelyn D. et al. The Drosophila 18 wheeler is required for morphogenesis and has striking similarities to Toll. Development 1994; 120: 885—899.

12.

Lemaitre B. , Kromer-Metzger E. , Michaut L. et al. A recessive mutation, immune deficiency (imd), defines two distinct control pathways in the Drosophila host defense . Proc Natl Acad Sci USA 1995; 92: 9365—9469.

13.

Hedengren M. , Asling B. , Dushay M. et al. Relish, a central factor in the control of humoral but not cellular immunity in Drosophila. Mol Cell 1999; 4: 1—20.

14.

Karin M. The beginning of the end: IkappaB kinase (IKK) and NFkappaB activation. J Biol Chem 1999; 274: 27339—27342.

15.

Lu Y. , Wu L. , Anderson K. The antibacterial arm of the Drosophila innate immune response requires an IκB kinase. Genes Dev 2001; 15: 104—110.

16.

Rutschmann S. , Jung A. , Zhou R. et al. Role of Drosophila IKKγ in an innate immune response independent of the Toll pathway. Nat Immunol 2000; 1: 342—347.

17.

Leulier F. , Rodriguez A. , Khush RS , Abrams JM , Lemaitre B. The Drosophila caspase Dredd is required to resist Gram-negative bacterial infection. EMBO Rep 2000; 1: 353—358.