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Legionella pp 371-397 | Cite as

The Caenorhabditis elegans Model of Legionella Infection

  • Ann Karen C. BrassingaEmail author
  • Costi D. Sifri
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1921)

Abstract

Caenorhabditis elegans can serve as a simple genetic host to study interactions between Legionellaceae and their hosts and to examine the contribution of specific gene products to virulence and immunity. C. elegans nematodes have several appealing attributes as a host organism; they are inexpensive, have robust genetic analysis tools, have a simple anatomy yet display a wide range of complex behaviors, and, as invertebrates, do not require animal ethics protocols. Use of C. elegans as a host model complements cell-based models, providing additional support and consistency of the experimental data obtained from multiple models. The C. elegans innate immune system functions similarly to that of the alveolar macrophage including the apoptosis [a.k.a. programmed cell death (PCD)] pathway located within the germline. The digestive tract of C. elegans is a primary interface between the innate immune system and bacterial pathogens. Thus, the C. elegans host model provides an alternative approach to investigate L. pneumophila immunopathogenesis, particularly in the view of the recent discovery of Legionella-containing vacuoles within the gonadal tissues of Legionella-colonized nematodes supporting the plausible evolutionary origin of the strategies employed by L. pneumophila to counteract macrophage cellular responses.

Key words

Caenorhabditis elegans Nematode Host model Innate immunity Survival assay Bacterial immunopathogenesis Human macrophage 

Notes

Acknowledgment

We thank Mathieu Pinette, Jacqueline Hellinga, Alexander Diamandas, and Dr. Jay Kormish for their contributions. This work was supported by a Howard Hughes Medical Institute Early Career Award to C.D.S., and a National Science and Engineering Council Discovery Grant, a Canadian Foundation for Innovation, a Manitoba Medical Service Foundation Award and a Manitoba Health Research Council Establishment Grant to A.K.C.B.

References

  1. 1.
    Sifri CD, Begun J, Ausubel FM (2005) The worm has turned—microbial virulence modeled in Caenorhabditis elegans. Trends Microbiol 13:119–127CrossRefGoogle Scholar
  2. 2.
    Hilbi H, Weber SS, Ragaz C et al (2007) Environmental predators as models for bacterial pathogenesis. Environ Microbiol 9:563–575CrossRefGoogle Scholar
  3. 3.
    Mellies JL, Lawrence-Pine ER (2010) Interkingdom signaling between pathogenic bacteria and Caenorhabditis elegans. Trends Microbiol 18:448–454CrossRefGoogle Scholar
  4. 4.
    Irazoqui JE, Urbach JM, Ausubel FM (2010) Evolution of host innate defence: insights from Caenorhabditis elegans and primitive invertebrates. Nat Rev Immunol 10:47–58CrossRefGoogle Scholar
  5. 5.
    Brenner S (1974) The genetics of Caenorhabditis elegans. Genetics 77:71–94PubMedPubMedCentralGoogle Scholar
  6. 6.
    Hope IA (ed) (1999) C. elegans: a practical approach. Oxford University Press, OxfordGoogle Scholar
  7. 7.
    Millet AC, Ewbank JJ (2004) Immunity in Caenorhabditis elegans. Curr Opin Immunol 16:4–9CrossRefGoogle Scholar
  8. 8.
    Nicholas HR, Hodgkin J (2004) Responses to infection and possible recognition strategies in the innate immune system of Caenorhabditis elegans. Mol Immunol 41:479–493CrossRefGoogle Scholar
  9. 9.
    Pujol N, Link EM, Liu LX et al (2001) A reverse genetic analysis of components of the Toll signaling pathway in Caenorhabditis elegans. Curr Biol 11:809–821CrossRefGoogle Scholar
  10. 10.
    Troemel ER, Chu SW, Reinke V et al (2006) p38 MAPK regulates expression of immune response genes and contributes to longevity in C. elegans. PLoS Genet 2:e183.  https://doi.org/10.1371/journal.pgen.0020183CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Schulenburg H, Ewbank JJ (2007) The genetics of pathogen avoidance in Caenorhabditis elegans. Mol Microbiol 66:563–570CrossRefGoogle Scholar
  12. 12.
    Pradel E, Zhang Y, Pujol N et al (2007) Detection and avoidance of a natural product from the pathogenic bacterium Serratia marcescens by Caenorhabditis elegans. Proc Natl Acad Sci U S A 104:2295–2300CrossRefGoogle Scholar
  13. 13.
    Tenor JL, Aballay A (2008) A conserved Toll-like receptor is required for Caenorhabditis elegans innate immunity. EMBO Rep 9:103–109CrossRefGoogle Scholar
  14. 14.
    Kim DH, Feinbaum R, Alloing G et al (2002) A conserved p38 MAP kinase pathway in Caenorhabditis elegans innate immunity. Science 297:623–626CrossRefGoogle Scholar
  15. 15.
    Garsin DA, Villanueva JM, Begun J et al (2003) Long-lived C. elegans daf-2 mutants are resistant to bacterial pathogens. Science 300:1921CrossRefGoogle Scholar
  16. 16.
    Aballay A, Yorgey P, Ausubel FM (2000) Salmonella typhimurium proliferates and establishes a persistent infection in the intestine of Caenorhabditis elegans. Curr Biol 10:1539–1542CrossRefGoogle Scholar
  17. 17.
    Kinchen JM, Hengartner MO (2005) Tales of cannibalism, suicide, and murder: Programmed cell death in C. elegans. Curr Top Dev Biol 65:1–45PubMedGoogle Scholar
  18. 18.
    Mizuno T, Hisamoto N, Terada T et al (2004) The Caenorhabditis elegans MAPK phosphatase VHP-1 mediates a novel JNK-like signaling pathway in stress response. EMBO J 23:2226–2234CrossRefGoogle Scholar
  19. 19.
    Darby C (2005) Interactions with microbial pathogens. In: WormBook (ed) The C. elegans research community, WormBook,  https://doi.org/10.1895/wormbook.1.21.1., http://www.wormbook.org
  20. 20.
    Caffrey DR, O’Neill LA, Shields DC (1999) The evolution of the MAP kinase pathways: coduplication of interacting proteins leads to new signaling cascades. J Mol Evol 49:567–582CrossRefGoogle Scholar
  21. 21.
    Plowman GD, Sudarsanam S, Bingham J et al (1999) The protein kinases of Caenorhabditis elegans: a model for signal transduction in the multicellular organisms. Proc Natl Acad Sci U S A 96:13603–13610CrossRefGoogle Scholar
  22. 22.
    Kim DH, Liberati NT, Mizuno T et al (2004) Integration of Caenorhabditis elegans MAPK pathways mediating immunity and stress resistance by MEK-1 MAPK kinase and VHP-1 MAPK phosphatase. Proc Natl Acad Sci U S A 101:10990–10994CrossRefGoogle Scholar
  23. 23.
    Brassinga AKC, Kinchen JM, Cupp ME et al (2010) Caenorhabditis is a metazoan host for Legionella. Cell Microbiol 12:343–361CrossRefGoogle Scholar
  24. 24.
    Welsh CT, Summersgill JT, Miller RD (2004) Increases in c-Jun N-Terminal kinase/stress-activated protein kinase and p38 activity in monocyte-derived macrophages following the uptake of Legionella pneumophila. Infect Immun 72:1512–1518CrossRefGoogle Scholar
  25. 25.
    Abu-Zant A, Santic M, Molmeret M et al (2005) Incomplete activation of macrophage apoptosis during intracellular replication of Legionella pneumophila. Infect Immun 73:5339–5349CrossRefGoogle Scholar
  26. 26.
    Alper S, Laws R, Lackford B et al (2008) Identification of innate immunity genes and pathways using a comparative genomics approach. Mol Cell Biol 27:5544–5553CrossRefGoogle Scholar
  27. 27.
    Hellinga JR, Garduño RA, Kormish JD, Tanner JR, Khan D, Buchko K, Jimenez C, Pinette MM, Brassinga AKC (2015) Identification of vacuoles containing extraintestinal differentiated forms of Legionella pneumophila in colonized Caenorhabditis elegans soil nematodes. Microbiologyopen 4:660–681CrossRefGoogle Scholar
  28. 28.
    Abnave P, Mottola G, Gimenez G, Boucherit N, Trouplin V, Torre C, Conti F, Amara AB, Lepolard C, Djian B, Hamaoui D, Mettouchi A, Kumar A, Pagnotta S, Bonatti S, Lepidi H, Salvetti A, Abi-Rached L, Lemichez E, Mege J-L, Ghigo E (2014) Screening in planarians identifies MORN2 as a key component in LC3-associated phagocytosis and resistance to bacterial infection. Cell Host Microbe 16:338–350CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of MicrobiologyUniversity of ManitobaWinnipegCanada
  2. 2.Division of Infectious Diseases and International Health, Department of MedicineUniversity of Virginia Health SystemCharlottesvilleUSA

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