Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Function of the drosophila pattern-recognition receptor PGRP-SD in the detection of Gram-positive bacteria

Abstract

The activation of an immune response requires recognition of microorganisms by host receptors. In drosophila, detection of Gram-positive bacteria is mediated by cooperation between the peptidoglycan-recognition protein-SA (PGRP-SA) and Gram-negative binding protein 1 (GNBP1) proteins. Here we show that some Gram-positive bacterial species activate an immune response in a PGRP-SA- and GNBP1-independent manner, indicating that alternative receptors exist. Consistent with this, we noted that PGRP-SD mutants were susceptible to some Gram-positive bacteria and that a loss-of-function mutation in PGRP-SD severely exacerbated the PGRP-SA and GNBP1 mutant phenotypes. These data indicate that PGRP-SD can function as a receptor for Gram-positive bacteria and shows partial redundancy with the PGRP-SA–GNBP1 complex.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Toll pathway activation in the absence of a functional PGRP-SA–GNBP1 receptor complex.
Figure 2: Effects of PGRP-SD mutation on Toll pathway activation by Gram-positive bacteria.
Figure 3: Effects of PGRP-SD and PGRP-SA mutations on Toll pathway activation by S. aureus peptidoglycan.
Figure 4: PGRP-SD mutant susceptibility to infection by Gram-positive bacteria.
Figure 5: PGRP-SD is not needed for detection of fungi or Gram-negative bacteria.

Similar content being viewed by others

References

  1. Bulet, P., Charlet, M. & Hetru, C. in Infectious disease: Innate Immunity (ed. Hoffmann, J.A. and Ezekowitz, R.A.B.) 89–107 (Human, Totowa, New Jersey, 2002).

    Google Scholar 

  2. Zasloff, M. Antimicrobial peptides of multicellular organisms. Nature 415, 389–395 (2002).

    Article  CAS  Google Scholar 

  3. De Gregorio, E., Spellman, P.T., Rubin, G.M. & Lemaitre, B. Genome-wide analysis of the Drosophila immune response by using oligonucleotide microarrays. Proc. Natl. Acad. Sci. USA 98, 12590–12595 (2001).

    Article  CAS  Google Scholar 

  4. Irving, P. et al. A genome-wide analysis of immune responses in Drosophila. Proc. Natl. Acad. Sci. USA 98, 15119–15124 (2001).

    Article  CAS  Google Scholar 

  5. Hoffmann, J.A. The immune response of Drosophila. Nature 426, 33–38 (2003).

    Article  CAS  Google Scholar 

  6. Brennan, C.A. & Anderson, K.V. Drosophila: the genetics of innate immune recognition and response. Annu. Rev. Immunol. 22, 457–483 (2004).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  8. Gobert, V. et al. Dual activation of the Drosophila Toll pathway by two pattern recognition receptors. Science 302, 2126–2130 (2003).

    Article  CAS  Google Scholar 

  9. Pili-Floury, S. et al. In vivo RNAi analysis reveals an unexpected role for GNBP1 in the defense against Gram-positive bacterial infection in Drosophila adults. J. Biol. Chem. 279, 12848–12853 (2004).

    Article  CAS  Google Scholar 

  10. Gottar, M. et al. The Drosophila immune response against Gram-negative bacteria is mediated by a peptidoglycan recognition protein. Nature 416, 640–644 (2002).

    Article  CAS  Google Scholar 

  11. Ramet, M., Manfruelli, P., Pearson, A., Mathey-Prevot, B. & Ezekowitz, R.A. Functional genomic analysis of phagocytosis and identification of a Drosophila receptor for E. coli. Nature 416, 644–648 (2002).

    Article  CAS  Google Scholar 

  12. Choe, K.M., Werner, T., Stoven, S., Hultmark, D. & Anderson, K.V. Requirement for a peptidoglycan recognition protein (PGRP) in Relish activation and antibacterial immune responses in Drosophila. Science 296, 359–362 (2002).

    Article  CAS  Google Scholar 

  13. Werner, T. et al. A family of peptidoglycan recognition proteins in the fruit fly Drosophila melanogaster. Proc. Natl. Acad. Sci. USA 97, 13772–13777 (2000).

    Article  CAS  Google Scholar 

  14. Leulier, F. et al. The Drosophila immune system detects bacteria through specific peptidoglycan recognition. Nat. Immunol. 4, 478–484 (2003).

    Article  CAS  Google Scholar 

  15. Yoshida, H., Kinoshita, K. & Ashida, M. Purification of a peptidoglycan recognition protein from hemolymph of the silkworm, Bombyx mori. J. Biol. Chem. 271, 13854–13860 (1996).

    Article  CAS  Google Scholar 

  16. Liu, C., Gelius, E., Liu, G., Steiner, H. & Dziarski, R. Mammalian peptidoglycan recognition protein binds peptidoglycan with high affinity, is expressed in neutrophils, and inhibits bacterial growth. J. Biol. Chem. 275, 24490–24499 (2000).

    Article  CAS  Google Scholar 

  17. Liu, C., Xu, Z., Gupta, D. & Dziarski, R. Peptidoglycan recognition proteins: a novel family of four human innate immunity pattern recognition molecules. J. Biol. Chem. 276, 34686–34694 (2001).

    Article  CAS  Google Scholar 

  18. Kang, D., Liu, G., Lundstrom, A., Gelius, E. & Steiner, H. A peptidoglycan recognition protein in innate immunity conserved from insects to humans. Proc. Natl. Acad. Sci. USA 95, 10078–10082 (1998).

    Article  CAS  Google Scholar 

  19. Tydell, C.C., Yount, N., Tran, D., Yuan, J. & Selsted, M.E. Isolation, characterization, and antimicrobial properties of bovine oligosaccharide-binding protein. A microbicidal granule protein of eosinophils and neutrophils. J. Biol. Chem. 277, 19658–19664 (2002).

    Article  CAS  Google Scholar 

  20. Steiner, H. Peptidoglycan recognition proteins: on and off switches for innate immunity. Immunol. Rev. 198, 83–96 (2004).

    Article  CAS  Google Scholar 

  21. Mellroth, P., Karlsson, J. & Steiner, H. A scavenger function for a Drosophila peptidoglycan recognition protein. J. Biol. Chem. 278, 7059–7064 (2003).

    Article  CAS  Google Scholar 

  22. Kim, M.S., Byun, M. & Oh, B.H. Crystal structure of peptidoglycan recognition protein LB from Drosophila melanogaster. Nat. Immunol. 4, 787–793 (2003).

    Article  CAS  Google Scholar 

  23. Gelius, E., Persson, C., Karlsson, J. & Steiner, H. A mammalian peptidoglycan recognition protein with N-acetylmuramoyl-L-alanine amidase activity. Biochem. Biophys. Res. Commun. 306, 988–994 (2003).

    Article  CAS  Google Scholar 

  24. Wang, Z.M. et al. Human peptidoglycan recognition protein-L is an N-acetylmuramoyl-L-alanine amidase. J. Biol. Chem. 278, 49044–49052 (2003).

    Article  CAS  Google Scholar 

  25. Bellen, H.J. et al. The BDGP gene disruption project: single transposon insertions associated with 40% of Drosophila genes. Genetics 167, 761–781 (2004).

    Article  CAS  Google Scholar 

  26. Lee, M.H. et al. Peptidoglycan recognition proteins involved in 1,3-β-D-glucan-dependent prophenoloxidase activation system of insect. J. Biol. Chem. 279, 3218–3227 (2004).

    Article  CAS  Google Scholar 

  27. Kaneko, T. et al. Monomeric and polymeric Gram-negative peptidoglycan but not purified LPS stimulate the Drosophila IMD pathway. Immunity 20, 637–649 (2004).

    Article  CAS  Google Scholar 

  28. Lemaitre, B., Nicolas, E., Michaut, L., Reichhart, J.M. & Hoffmann, J.A. The dorsoventral regulatory gene cassette spatzle/Toll/cactus controls the potent antifungal response in Drosophila adults. Cell 86, 973–983 (1996).

    Article  CAS  Google Scholar 

  29. Rutschmann, S., Kilinc, A. & Ferrandon, D. Cutting edge: the toll pathway is required for resistance to gram-positive bacterial infections in Drosophila. J. Immunol. 168, 1542–1546 (2002).

    Article  CAS  Google Scholar 

  30. Rutschmann, S. et al. Role of Drosophila IKK γ in a toll-independent antibacterial immune response. Nat. Immunol. 1, 342–347 (2000).

    Article  CAS  Google Scholar 

  31. Weber, A.N. et al. Binding of the Drosophila cytokine Spatzle to Toll is direct and establishes signaling. Nat. Immunol. 4, 794–800 (2003).

    Article  CAS  Google Scholar 

  32. Schleifer, K. & Kandelr, P. Peptidoglycan types of bacterial cell walls and their taxonomic implications. Bacteriol. Rev. 36, 407–477 (1972).

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Tauszig-Delamasure, S., Bilak, H., Capovilla, M., Hoffmann, J.A. & Imler, J.L. Drosophila MyD88 is required for the response to fungal and Gram-positive bacterial infections. Nat. Immunol. 3, 91–97 (2002).

    Article  CAS  Google Scholar 

  34. de Jonge BL, C.Y., Gage D, Tomasz A. Peptidoglycan composition of a highly methicillin-resistant Staphylococcus aureus strain. The role of penicillin binding protein 2A. J. Biol. Chem. 267, 11248–11254 (2004).

    Google Scholar 

  35. Girardin, S.E. et al. Nod2 is a general sensor of peptidoglycan through muramyl dipeptide (MDP) detection. J. Biol. Chem. 278, 8869–8872 (2003).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank S. Ozkan and M.C. Lacombe for technical help; F. Dromer for the C. neoformans strain; and M. Meister for comments on the manuscript. Supported by Centre National de la Recherche Scientifique, the Ministère de l'Education Nationale de la Recherche et de la Technologie, the Fondation pour la Recherche Médicale and the National Institutes of Health.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Julien Royet.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1

Molecular characterisation of PGRP-SD protein null mutants. (PDF 25 kb)

Supplementary Fig. 2

PGRP-SD mRNA level in PGRP-SA;PGRP-SD double mutant flies over-expressing the PGRP-SD cDNA. (PDF 21 kb)

Supplementary Fig. 3

Effects of PGRP-SA, GNBP-1 and PGRP-SD overexpression on Toll pathway activation. (PDF 24 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bischoff, V., Vignal, C., Boneca, I. et al. Function of the drosophila pattern-recognition receptor PGRP-SD in the detection of Gram-positive bacteria. Nat Immunol 5, 1175–1180 (2004). https://doi.org/10.1038/ni1123

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ni1123

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing