Innate Immunity in C. elegans

Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 708)


The nematode Caenorhabditis elegans is proving to be a powerful invertebrate model to study host-pathogen interactions. In common with other invertebrates, C. elegans relies solely on its innate immune system to defend itself against pathogens. Studies of the nematode response to infection with various fungal and bacterial pathogens have revealed that the innate immune system of C. elegans employs evolutionary conserved signalling pathways. They regulate the expression of various effectors molecules, some of which are also conserved. Here, we summarize the current knowledge of the pathways and effector molecules involved in the nematode immune response, with a particular focus on the antifungal immune response of the C. elegans epidermis.


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  1. 1.
    Barrière A, Felix MA. Isolation of C. elegans and related nematodes. The C. elegans Research Community: WormBook; 2006.Google Scholar
  2. 2.
    Fares H, Greenwald I. Genetic analysis of endocytosis in Caenorhabditis elegans: coelomocyte uptake defective mutants. Genetics 2001; 159(1):133–145.PubMedGoogle Scholar
  3. 3.
    Schulenburg H, Ewbank JJ. The genetics of pathogen avoidance in Caenorhabditis elegans. Mol Microbiol 2007; 66(3): 563–570.PubMedCrossRefGoogle Scholar
  4. 4.
    Pradel E, Zhang Y, Pujol N et al. Detection and avoidance of a natural product from the pathogenic bacterium Serratia marcescens by Caenorhabditis elegans. Proc Natl Acad Sci USA 104(7):2295–2300.Google Scholar
  5. 5.
    Pujol N, Link EM, Liu LX et al. A reverse genetic analysis of components of the Toll signalling pathway in Caenorhabditis elegans. Curr Biol 2001; 11(11):809–821.PubMedCrossRefGoogle Scholar
  6. 6.
    Remy JJ, Hobert O. An interneuronal chemoreceptor required for olfactory imprinting in C. elegans. Science (New York, NY) 2005; 309(5735):787–790.CrossRefGoogle Scholar
  7. 7.
    Zhang Y, Lu H, Bargmann CI. Pathogenic bacteria induce aversive olfactory learning in Caenorhabditis elegans. Nature 2005; 438(7065):179–184.PubMedCrossRefGoogle Scholar
  8. 8.
    Wes PD, Bargmann CI. C. elegans odour discrimination requires asymmetric diversity in olfactory neurons. Nature 2001; 410(6829):698–701.PubMedCrossRefGoogle Scholar
  9. 9.
    Chuang CF, Bargmann CI. A Toll-interleukin 1 repeat protein at the synapse specifies asymmetric odorant receptor expression via ASK1 MAPKKK signaling. Genes Dev 2005; 19(2):270–281.PubMedCrossRefGoogle Scholar
  10. 10.
    Shivers RP, Kooistra T, Chu SW et al. Tissue-specific activities of an immune signaling module regulate physiological responses to pathogenic and nutritional bacteria in C. elegans. Cell Host Microbe 2009; 6(4):321–330.PubMedCrossRefGoogle Scholar
  11. 11.
    Labrousse A, Chauvet S, Couillault C et al. Caenorhabditis elegans is a model host for Salmonella typhimurium. Curr Biol 2000; 10(23):1543–1545.PubMedCrossRefGoogle Scholar
  12. 12.
    Kim DH, Feinbaum R, Alloing G et al. A conserved p38 MAP kinase pathway in Caenorhabditis elegans innate immunity. Science (New York, NY) 2002; 297(5581):623–626.CrossRefGoogle Scholar
  13. 13.
    Kurz CL, Chauvet S, Andres E et al. Virulence factors of the human opportunistic pathogen Serratia marcescens identified by in vivo screening. EMBO J 2003; 22(7):1451–1460.PubMedCrossRefGoogle Scholar
  14. 14.
    Borgonie G, Claeys M, Leyns F et al. Effect of nematicidal Bacillus thuringiensis strains on free-living nematodes. 1. Light microscopic observations, species and biological stage specificity and identification of resistant mutants of Caenorhabditis elegans. Fundam appl Nematol 1996; 19(4):391–398.Google Scholar
  15. 15.
    Troemel ER, Felix MA, Whiteman NK et al. Microsporidia are natural intracellular parasites of the nematode Caenorhabditis elegans. PLoS Biol 2008; 6(12):2736–2752.PubMedCrossRefGoogle Scholar
  16. 16.
    Jia K, Thomas C, Akbar M et al. Autophagy genes protect against Salmonella typhimurium infection and mediate insulin signaling-regulated pathogen resistance. Proc Natl Acad Sci USA 2009; 106(34): 14564–14569.PubMedGoogle Scholar
  17. 17.
    Hodgkin J, Kuwabara PE, Corneliussen B. A novel bacterial pathogen, Microbacterium nematophilum, induces morphological change in the nematode C. elegans. Curr Biol 2000; 10(24):1615–1618.PubMedCrossRefGoogle Scholar
  18. 18.
    Muir RE, Tan MW. Leucobacter chromiireducens subsp. solipictus Exerts Virulence on Caenorhabditis elegans, Characterization of a Novel Host-Pathogen Interaction. Appl Environ Microbiol 2008.Google Scholar
  19. 19.
    Barron GL. Nematophagous destroying fungi. Topics in Mycobiology [serial on the Internet] 1977; 1.Google Scholar
  20. 20.
    Jansson HB. Adhesion of conidia of Drechmeria coniospora to Caenorhabditis elegans wild type and mutants. J Nematol 1994; 26:430–435.PubMedGoogle Scholar
  21. 21.
    Gallagher LA, Manoil C. Pseudomonas aeruginosa PAO1 kills Caenorhabditis elegans by cyanide poisoning. J Bacteriol 2001; 183(21):6207–6214.PubMedCrossRefGoogle Scholar
  22. 22.
    Akira S, Uematsu S, Takeuchi O. Pathogen recognition and innate immunity. Cell 2006; 124(4):783–801.PubMedCrossRefGoogle Scholar
  23. 23.
    Palm NW, Medzhitov R. Pattern recognition receptors and control of adaptive immunity. Immunol Rev 2009; 227(1):221–233.PubMedCrossRefGoogle Scholar
  24. 24.
    Couillault C, Pujol N, Reboul J et al. TLR-independent control of innate immunity in Caenorhabditis elegans by the TIR domain adaptor protein TIR-1, an ortholog of human SARM. Nature immunology 2004; 5:488–494.PubMedCrossRefGoogle Scholar
  25. 25.
    Tenor JL, Aballay A. A conserved Toll-like receptor is required for Caenorhabditis elegans innate immunity. EMBO Rep 2008; 9(1): 103–109.PubMedCrossRefGoogle Scholar
  26. 26.
    Powell JR, Kim DH, Ausubel FM. The G protein-coupled receptor FSHR-1 is required for the Caenorhabditis elegans innate immune response. Proc Natl Acad Sci USA 2009; 106(8):2782–2787.PubMedCrossRefGoogle Scholar
  27. 27.
    Gordon S. Pattern recognition receptors. Doubling up for the innate immune response. Cell 2002; 111(7):927–930.PubMedCrossRefGoogle Scholar
  28. 28.
    Nicholas HR, Hodgkin J. Responses to infection and possible recognition strategies in the innate immune system of Caenorhabditis elegans. Mol Immunol 2004; 41(5):479–493.PubMedCrossRefGoogle Scholar
  29. 29.
    Means TK, Mylonakis E, Tampakakis E et al. Evolutionarily conserved recognition and innate immunity to fungal pathogens by the scavenger receptors SCARF1 and CD36. J Exp Med 2009.Google Scholar
  30. 30.
    Matzinger P. The danger model: a renewed sense of self. Science (New York, NY) 2002; 296(5566):301–305.Google Scholar
  31. 31.
    Schulenburg H, Hoeppner MP, Weiner J 3rd et al. Specificity of the innate immune system and diversity of C-type lectin domain (CTLD) proteins in the nematode Caenorhabditis elegans. Immunobiology 2008; 213(3–4):237–250.PubMedCrossRefGoogle Scholar
  32. 32.
    Wong D, Bazopoulou D, Pujol N et al. Genome-wide investigation reveals pathogen-specific and shared signatures in the response of Caenorhabditis elegans to infection. Genome Biol 2007; 8(9):R194.PubMedCrossRefGoogle Scholar
  33. 33.
    Sifri CD, Begun J, Ausubel FM et al. Caenorhabditis elegans as a model host for Staphylococcus aureus pathogenesis. Infect Immun 2003; 71(4):2208–2217.PubMedCrossRefGoogle Scholar
  34. 34.
    Liberati NT, Fitzgerald KA, Kim DH et al. Requirement for a conserved Toll/interleukin-1 resistance domain protein in the Caenorhabditis elegans immune response. Proc Natl Acad Sci USA 2004; 101(17):6593–6598.PubMedCrossRefGoogle Scholar
  35. 35.
    Pujol N, Cypowyj S, Ziegler K et al. Distinct innate immune responses to infection and wounding in the C. elegans epidermis. Curr Biol 2008; 18(7):481–489.PubMedCrossRefGoogle Scholar
  36. 36.
    Begun J, Gaiani JM, Rohde H et al. Staphylococcal biofilm exopolysaccharide protects against Caenorhabditis elegans immune defenses. PLoS Pathog 2007; 3(4):e57.PubMedCrossRefGoogle Scholar
  37. 37.
    Aballay A, Drenkard E, Hilbun LR et al. Caenorhabditis elegans innate immune response triggered by Salmonella enterica requires intact LPS and is mediated by a MAPK signaling pathway. Curr Biol 2003; 13(1):47–52.PubMedCrossRefGoogle Scholar
  38. 38.
    Huffman DL, Abrami L, Sasik R et al. Mitogen-activated protein kinase pathways defend against bacterial pore-forming toxins. Proc Natl Acad Sci USA 2004; 101(30):10995–11000.PubMedCrossRefGoogle Scholar
  39. 39.
    Nicholas HR, Hodgkin J. The ERK MAP kinase cascade mediates tail swelling and a protective response to rectal infection in C. elegans. Curr Biol 2004; 14(14):1256–1261.PubMedCrossRefGoogle Scholar
  40. 40.
    Kim DH, Liberati NT, Mizuno T et al. 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 USA 2004; 101(30): 10990–10994.PubMedCrossRefGoogle Scholar
  41. 41.
    Lin K, Hsin H, Libina N et al. Regulation of the Caenorhabditis elegans longevity protein DAF-16 by insulin/IGF-1 and germline signaling. Nat Genet 2001; 28(2):139–145.PubMedCrossRefGoogle Scholar
  42. 42.
    Garsin DA, Villanueva JM, Begun J et al. Long-lived C. elegans daf-2 mutants are resistant to bacterial pathogens. Science (New York, NY) 2003; 300(5627):1921.CrossRefGoogle Scholar
  43. 43.
    Evans EA, Chen WC, Tan MW. The DAF-2 Insulin-like signaling pathway independently regulates aging and immunity in C. elegans. Aging Cell 2008; 7(6):879–893.PubMedCrossRefGoogle Scholar
  44. 44.
    Murphy CT, McCarroll SA, Bargmann CI et al. Genes that act downstream of DAF-16 to influence the lifespan of Caenorhabditis elegans. Nature 2003; 424(6946):277–283.PubMedCrossRefGoogle Scholar
  45. 45.
    Shapira M, Hamlin B J, Rong J et al. A conserved role for a GATA transcription factor in regulating epithelial innate immune responses. Proc Natl Acad Sci USA 2006; 103(38):14086–14091.PubMedCrossRefGoogle Scholar
  46. 46.
    Troemel ER, Chu SW, Reinke V et al. p38 MAPK regulates expression of immune response genes and contributes to longevity in C. elegans. PLoS Genetics 2006; 2(11):e183.PubMedCrossRefGoogle Scholar
  47. 47.
    Alper S, McBride SJ, Lackford B et al. Specificity and complexity of the Caenorhabditis elegans innate immune response. Mol Cell Biol 2007; 27(15):5544–5553.PubMedCrossRefGoogle Scholar
  48. 48.
    Hasshoff M, Bohnisch C, Tonn D et al. The role of Caenorhabditis elegans insulin-like signaling in the behavioral avoidance of pathogenic Bacillus thuringiensis. FASEB J 2007; 21(8):1801–1812.PubMedCrossRefGoogle Scholar
  49. 49.
    Todd DJ, Lee AH, Glimcher LH. The endoplasmic reticulum stress response in immunity and autoimmunity. Nat Rev Immunol 2008; 8(9):663–674.PubMedCrossRefGoogle Scholar
  50. 50.
    Bischof LJ, Kao CY, Los FC et al. Activation of the unfolded protein response is required for defenses against bacterial pore-forming toxin in vivo. PLoS Pathog 2008; 4(10):e1000176.PubMedCrossRefGoogle Scholar
  51. 51.
    Haskins KA, Russell JF, Gaddis N et al. Unfolded protein response genes regulated by CED-1 are required for Caenorhabditis elegans innate immunity. Dev Cell 2008; 15(1):87–97.PubMedCrossRefGoogle Scholar
  52. 52.
    Richardson CE, Kooistra T, Kim DH. An essential role for XBP-1 in host protection against immune activation in C. elegans. Nature 2010; 463(6784): 1092–1095.PubMedCrossRefGoogle Scholar
  53. 53.
    Mochii M, Yoshida S, Morita K et al. Identification of transforming growth factor-beta-regulated genes in Caenorhabditis elegans by differential hybridization of arrayed cDNAs. Proc Natl Acad Sci USA 1999; 96(26):15020–15025.PubMedCrossRefGoogle Scholar
  54. 54.
    Mallo GV, Kurz CL, Couillault C et al. Inducible antibacterial defense system in C. elegans. Curr Biol 2002; 12(14):1209–1214.PubMedCrossRefGoogle Scholar
  55. 55.
    Zugasti O, Ewbank JJ. Neuroimmune regulation of antimicrobial peptide expression by a noncanonical TGF-beta signaling pathway in Caenorhabditis elegans epidermis. Nature immunology 2009; 10(3):249–256.PubMedCrossRefGoogle Scholar
  56. 56.
    Hashimoto Y, Ookuma S, Nishida E. Lifespan extension by suppression of autophagy genes in Caenorhabditis elegans. Genes Cells 2009; 14(6):717–726.PubMedCrossRefGoogle Scholar
  57. 57.
    Kerry S, Tekippe M, Gaddis NC et al. GATA transcription factor required for immunity to bacterial and fungal pathogens. PLoS ONE 2006; 1:e77.PubMedCrossRefGoogle Scholar
  58. 58.
    Pujol N, Zugasti O, Wong D et al. Anti-fungal innate immunity in C. elegans is enhanced by evolutionary diversification of antimicrobial peptides. PLoS Pathog 2008; 4(7):e1000105.PubMedCrossRefGoogle Scholar
  59. 59.
    Rohlfing AK, Miteva Y, Hannenhalli S et al. Genetic and physiological activation of osmosensitive gene expression mimics transcriptional signatures of pathogen infection in C. elegans. PLoS One 2010; 5(2):e9010.PubMedCrossRefGoogle Scholar
  60. 60.
    Singh V, Aballay A. Heat-shock transcription factor (HSF)-1 pathway required for Caenorhabditis elegans immunity. Proc Natl Acad Sci USA 2006; 103(35): 13092–13097.PubMedCrossRefGoogle Scholar
  61. 61.
    Irazoqui JE, Ng A, Xavier RJ et al. Role for beta-catenin and HOX transcription factors in Caenorhabditis elegans and mammalian host epithelial-pathogen interactions. Proc Natl Acad Sci USA 2008; 105(45): 17469–17474.PubMedCrossRefGoogle Scholar
  62. 62.
    Chisholm A. Control of cell fate in the tail region of C. elegans by the gene egl-5. Development 1991; 111(4):921–932.PubMedGoogle Scholar
  63. 63.
    Nicholas HR, Hodgkin J. The C. elegans Hox gene egl-5 is required for correct development of the hermaphrodite hindgut and for the response to rectal infection by Microbacterium nematophilum. Dev Biol 2009; 329(1): 16–24.PubMedCrossRefGoogle Scholar
  64. 64.
    Gravato-Nobre MJ, Nicholas HR, Nijland R et al. Multiple genes affect sensitivity of Caenorhabditis elegans to the bacterial pathogen Microbacterium nematophilum. Genetics 2005; 171(3): 1033–1045.PubMedCrossRefGoogle Scholar
  65. 65.
    Estes KA, Dunbar TL, Powell JR et al. bZIP transcription factor zip-2 mediates an early response to Pseudomonas aeruginosa infection in Caenorhabditis elegans. Proc Natl Acad Sci USA 2010; 107(5):2153–2158.PubMedCrossRefGoogle Scholar
  66. 66.
    Kato Y, Aizawa T, Hoshino H et al. abf-1 and abf-2, ASABF-type antimicrobial peptide genes in Caenorhabditis elegans. Biochem J 2002; 361(Pt 2):221–230.PubMedCrossRefGoogle Scholar
  67. 67.
    Alegado RA, Tan MW. Resistance to antimicrobial peptides contributes to persistence of Salmonella typhimurium in the C. elegans intestine. Cell Microbiol 2008; 10(6):1259–1273.PubMedCrossRefGoogle Scholar
  68. 68.
    Roeder T, Stanisak M, Gelhaus C et al. Caenopores are antimicrobial peptides in the nematode Caenorhabditis elegans instrumental in nutrition and immunity. Developmental and comparative immunology 2009.Google Scholar
  69. 69.
    Banyai L, Patthy L. Amoebapore homologs of Caenorhabditis elegans. Biochim Biophys Acta 1998; 1429(1):259–264.PubMedCrossRefGoogle Scholar
  70. 70.
    Schulenburg H, Boehnisch C. Diversification and adaptive sequence evolution of Caenorhabditis lysozymes (Nematoda: Rhabditidae). BMC Evol Biol 2008; 8:114.PubMedCrossRefGoogle Scholar
  71. 71.
    Nandakumar M, Tan MW. Gamma-linolenic and stearidonic acids are required for basal immunity in Caenorhabditis elegans through their effects on p38 MAP kinase activity. PLoS Genet 2008; 4(11):e1000273.PubMedCrossRefGoogle Scholar
  72. 72.
    O’Rourke D, Baban D, Demidova M et al. Genomic clusters, putative pathogen recognition molecules and antimicrobial genes are induced by infection of C. elegans with M. nematophilum. Genome Res 2006; 16(8):1005–1016.PubMedCrossRefGoogle Scholar
  73. 73.
    Ideo H, Fukushima K, Gengyo-Ando K et al. A Caenorhabditis elegans glycolipid-binding galectin functions in host defense against bacterial infection. J Biol Chem 2009; 284(39):26493–26501.PubMedCrossRefGoogle Scholar
  74. 74.
    Chavez V, Mohri-Shiomi A, Maadani A et al. Oxidative stress enzymes are required for DAF-16-mediated immunity due to generation of reactive oxygen species by Caenorhabditis elegans. Genetics 2007; 176(3):1567–1577.PubMedCrossRefGoogle Scholar
  75. 75.
    Chavez V, Mohri-Shiomi A, Garsin DA. Ce-Duox1/BLI-3 generates reactive oxygen species as a protective innate immune mechanism in Caenorhabditis elegans. Infect Immun 2009; 77(11):4983–4989.PubMedCrossRefGoogle Scholar
  76. 76.
    Kawli T, Tan MW. Neuroendocrine signals modulate the innate immunity of Caenorhabditis elegans through insulin signaling. Nature immunology 2008; 9(12): 1415–1424.PubMedCrossRefGoogle Scholar
  77. 77.
    Styer KL, Singh V, Macosko E et al. Innate immunity in Caenorhabditis elegans is regulated by neurons expressing NPR-1/GPCR. Science (New York, NY) 2008; 322(5900):460–464.PubMedCrossRefGoogle Scholar
  78. 78.
    Reddy KC, Andersen EC, Kruglyak L et al. A polymorphism in npr-1 is abehavioral determinant of pathogen susceptibility in C. elegans. Science (New York, NY) 2009; 323(5912):382–384.CrossRefGoogle Scholar
  79. 79.
    Griffitts JS, Haslam SM, Yang T et al. Glycolipids as receptors for Bacillus thuringiensis crystal toxin. Science (New York, NY.) 2005; 307(5711):922–925.CrossRefGoogle Scholar
  80. 80.
    Bellier A, Chen CS, Kao CY et al. Hypoxia and the hypoxic response pathway protect against pore-forming toxins in C. elegans. PLoS Pathog 2009; 5(12):e1000689.PubMedCrossRefGoogle Scholar
  81. 81.
    Tong A, Lynn G, Ngo V et al. Negative regulation of Caenorhabditis elegans epidermal damage responses by death-associated protein kinase. Proc Natl Acad Sci USA 2009; 106(5):1457–1461.PubMedCrossRefGoogle Scholar
  82. 82.
    Ziegler K, Kurz CL, Cypowyj S et al. Antifungal innate immunity in C. elegans: PKCdelta links G protein signaling and a conserved p38 MAPK cascade. Cell Host Microbe 2009; 5(4):341–352.PubMedCrossRefGoogle Scholar
  83. 83.
    Miyata S, Begun J, Troemel ER et al. DAF-16-dependent suppression of immunity during reproduction in Caenorhabditis elegans. Genetics 2008; 178(2):903–918.PubMedCrossRefGoogle Scholar
  84. 84.
    Lee KZ, Kniazeva M, Han M et al. The fatty acid synthase fasn-1 acts upstream of WNK and Ste20/GCK-VI kinases to modulate antimicrobial peptide expression in C. elegans epidermis. Virulence 2010; 1(3).Google Scholar
  85. 85.
    Evans EA, Kawli T, Tan MW. Pseudomonas aeruginosa suppresses host immunity by activating the DAF-2 insulin-like signaling pathway in Caenorhabditis elegans. PLoS Pathog 2008; 4(10):e1000175.PubMedCrossRefGoogle Scholar
  86. 86.
    Partridge FA, Gravato-Nobre MJ, Hodgkin J. Signal transduction pathways that function in both development and innate immunity. Dev Dyn 2010.Google Scholar
  87. 87.
    Ren M, Feng H, Fu Y et al. Protein kinase D (DKF-2), a diacylglycerol effector, is an essential regulator of C. elegans innate immunity. Immunity 2009; 30(4):521–532.PubMedCrossRefGoogle Scholar
  88. 88.
    Kurz CL, Shapira M, Chen K et al. Caenorhabditis elegans pgp-5 is involved in resistance to bacterial infection and heavy metal and its regulation requires TIR-1 and a p38 map kinase cascade. Biochem Biophys Res Commun 2007; 363(2):438–443.PubMedCrossRefGoogle Scholar
  89. 89.
    Yook K, Hodgkin J. Mos1 Mutagenesis Reveals a Diversity of Mechanisms Affecting Response of Caenorhabditis elegans to the Bacterial Pathogen Microbacterium nematophilum. Genetics 2007; 175(2):681–697.PubMedCrossRefGoogle Scholar

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© Landes Bioscience and Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Centre d’Immunologie de Marseille-LuminyUniversité de la MéditerranéeMarseilleFrance

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