Tick as a Model for the Study of a Primitive Complement System

Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 710)


Ticks are blood feeding parasites transmitting a wide variety of pathogens to their vertebrate hosts. The transmitted pathogens apparently evolved efficient mechanisms enabling them to evade or withstand the cellular or humoral immune responses within the tick vector. Despite its importance, our knowledge of tick innate immunity still lags far beyond other well established invertebrate models, such as drosophila, horseshoe crab or mosquitoes. However, the recent release of the American deer tick, Ixodes scapularis, genome and feasibility of functional analysis based on RNA interference (RNAi) facilitate the development of this organism as a full-value model for deeper studies of vector-pathogen interactions.


Lyme Disease Tick Species Horseshoe Crab Hard Tick Soft Tick 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This work was supported by grant P506/110/2136 to P.K. from the Grant Agency of the Czech Republic, the Research Centre LC06009 and Research projects Z60220518 and MSMT6007665801 from Ministry of Education, Youth, and Sports of the Czech Republic.


  1. Ariki S, Takahara S, Shibata T et al (2008) Factor C acts as a lipopolysaccharide-responsive C3 convertase in horseshoe crab complement activation. J Immunol 181:7994–8001PubMedGoogle Scholar
  2. Armstrong PB (2010) Role of α2-macroglobulin in the immune response of invertebrates. Invert Surviv J 7:165–180Google Scholar
  3. Barker SC, Murell A (2008) Systematics and evolution of ticks with a list of valid genus and species names. In: Bowman AS, Nuttall PA (eds) Ticks: biology, disease and control. Cambridge University Press, Cambridge/New York, pp 1–39CrossRefGoogle Scholar
  4. Baxter RH, Chang CI, Chelliah Y et al (2007) Structural basis for conserved complement factor-like function in the antimalarial protein TEP1. Proc Natl Acad Sci USA 104:11615–11620PubMedCrossRefGoogle Scholar
  5. Bell-Sakyi L, Zweygarth E, Blouin EF et al (2007) Tick cell lines: tools for tick and tick-borne disease research. Trends Parasitol 23:450–457PubMedCrossRefGoogle Scholar
  6. Bishop R, Musoke A, Skilton R (2008) Theileria: life cycle stages associated with the ixodid tick vector. In: Bowman AS, Nuttall PA (eds) Ticks: biology, disease and control. Cambridge University Press, New York, pp 308–324CrossRefGoogle Scholar
  7. Blandin S, Levashina EA (2004) Thioester-containing proteins and insect immunity. Mol Immunol 40:903–908PubMedCrossRefGoogle Scholar
  8. Blandin S, Shiao SH, Moita LF et al (2004) Complement-like protein TEP1 is a determinant of vectorial capacity in the malaria vector Anopheles gambiae. Cell 116:661–670PubMedCrossRefGoogle Scholar
  9. Blandin SA, Marois E, Levashina EA (2008) Antimalarial responses in Anopheles gambiae: from a complement-like protein to a complement-like pathway. Cell Host Microbe 3:364–374PubMedCrossRefGoogle Scholar
  10. Blouin EF, de la Fuente J, Garcia-Garcia JC et al (2002) Applications of a cell culture system for studying the interaction of Anaplasma marginale with tick cells. Anim Health Res Rev 3:57–68PubMedCrossRefGoogle Scholar
  11. Borovickova B, Hypsa V (2005) Ontogeny of tick hemocytes: a comparative analysis of Ixodes ricinus and Ornithodoros moubata. Exp Appl Acarol 35:317–333PubMedCrossRefGoogle Scholar
  12. Buresova V (2009) Function of the α2-macroglobulin protein family in the immune response of the tick Ixodes ricinus [Ph.D.]. Ceske Budejovice. Faculty of Science, University of South BohemiaGoogle Scholar
  13. Buresova V, Franta Z, Kopacek P (2006) A comparison of Chryseobacterium indologenes pathogenicity to the soft tick Ornithodoros moubata and hard tickIxodes ricinus. J Invertebr Pathol 93:96–104PubMedCrossRefGoogle Scholar
  14. Buresova V, Hajdusek O, Franta Z et al (2009) IrAM-An alpha2-macroglobulin from the hard tick Ixodes ricinus: characterization and function in phagocytosis of a potential pathogen Chryseobacterium indologenes. Dev Comp Immunol 33:489–498PubMedCrossRefGoogle Scholar
  15. Chauvin A, Moreau E, Bonnet S et al (2009) Babesia and its hosts: adaptation to long-lasting interactions as a way to achieve efficient transmission. Vet Res 40:37PubMedCrossRefGoogle Scholar
  16. Coleman JL, Gebbia JA, Piesman J (1997) Plasminogen is required for efficient dissemination of B. burgdorferi in ticks and for enhancement of spirochetemia in mice. Cell 89:1111–1119PubMedCrossRefGoogle Scholar
  17. de la Fuente J, Kocan KM, Almazan C et al (2007) RNA interference for the study and genetic manipulation of ticks. Trends Parasitol 23:427–433PubMedCrossRefGoogle Scholar
  18. de la Fuente J, Estrada-Pena A, Venzal JM et al (2008a) Overview: ticks as vectors of pathogens that cause disease in humans and animals. Front Biosci 13:6938–6946PubMedCrossRefGoogle Scholar
  19. de la Fuente J, Kocan KM, Almazan C et al (2008b) Targeting the tick-pathogen interface for novel control strategies. Front Biosci 13:6947–6956PubMedCrossRefGoogle Scholar
  20. de Silva AM, Tyson KR, Pal U (2009) Molecular characterization of the tick-Borrelia interface. Front Biosci 14:3051–3063PubMedCrossRefGoogle Scholar
  21. Doan N, Gettins PG (2007) Human alpha2-macroglobulin is composed of multiple domains, as predicted by homology with complement component C3. Biochem J 407:23–30PubMedCrossRefGoogle Scholar
  22. Dodds AW, Day AJ (1996) Complement-related proteins in invertebrates. In: Soderhall K, Iwanaga S, Vasta GR (eds) New directions in invertebrate immunology. SOS Publications, Fair Haven, pp 303–342Google Scholar
  23. Endo Y, Takahashi M, Fujita T (2006) Lectin complement system and pattern recognition. Immunobiology 211:283–293PubMedCrossRefGoogle Scholar
  24. Ferrandon D, Imler JL, Hetru C et al (2007) The Drosophila systemic immune response: sensing and signalling during bacterial and fungal infections. Nat Rev Immunol 7:862–874PubMedCrossRefGoogle Scholar
  25. Francischetti IM, Sa-Nunes A, Mans BJ et al (2009) The role of saliva in tick feeding. Front Biosci 14:2051–2088PubMedCrossRefGoogle Scholar
  26. Gokudan S, Muta T, Tsuda R et al (1999) Horseshoe crab acetyl group-recognizing lectins involved in innate immunity are structurally related to fibrinogen. Proc Natl Acad Sci USA 96:10086–10091PubMedCrossRefGoogle Scholar
  27. Grubhoffer L, Rego ROM, Hajdušek O et al (2008) Tick lectins and fibrinogen-related proteins. In: Bowman AS, Nuttall PA (eds) Ticks: biology, disease and control. Cambridge University Press, Cambridge/New York, pp 127–142CrossRefGoogle Scholar
  28. Hovius JW, van Dam AP, Fikrig E (2007) Tick-host-pathogen interactions in Lyme borreliosis. Trends Parasitol 23:434–438PubMedCrossRefGoogle Scholar
  29. Inoue N, Hanada K, Tsuji N et al (2001) Characterization of phagocytic hemocytes in Ornithodoros moubata (Acari: Ixodidae). J Med Entomol 38:514–519PubMedCrossRefGoogle Scholar
  30. Iwanaga S, Lee BL (2005) Recent advances in the innate immunity of invertebrate animals. J Biochem Mol Biol 38:128–150PubMedCrossRefGoogle Scholar
  31. Janssen BJ, Huizinga EG, Raaijmakers HC et al (2005) Structures of complement component C3 provide insights into the function and evolution of immunity. Nature 437:505–511PubMedCrossRefGoogle Scholar
  32. Jongejan F, Uilenberg G (2004) The global importance of ticks. Parasitology 129(Suppl):S3–14PubMedGoogle Scholar
  33. Kawabata S, Tsuda R (2002) Molecular basis of non-self recognition by the horseshoe crab tachylectins. Biochim Biophys Acta 1572:414–421PubMedCrossRefGoogle Scholar
  34. Kawabata S, Koshiba T, Shibata T (2009) The lipopolysaccharide-activated innate immune response network of the horseshoe crab. Invert Surviv J 6:59–77Google Scholar
  35. Kocan KM, de la Fuente J, Blouin EF (2008) Advances toward understanding the molecular biology of the Anaplasma-tick interface. Front Biosci 13:7032–7045PubMedCrossRefGoogle Scholar
  36. Kopacek P, Weise C, Saravanan T et al (2000) Characterization of an alpha-macroglobulin-like glycoprotein isolated from the plasma of the soft tick Ornithodoros moubata. Eur J Biochem 267:465–475PubMedCrossRefGoogle Scholar
  37. Kopacek P, Hajdusek O, Buresova V et al (2010) Tick innate immunity. In: Soderhall K (ed) Invertebrate immunity. Landes Bioscience and Springer Science  +  Business Media, New York, pp 137–162Google Scholar
  38. Kovar V, Kopacek P, Grubhoffer L (2000) Isolation and characterization of Dorin M, a lectin from plasma of the soft tick Ornithodoros moubata. Insect Biochem Mol Biol 30:195–205PubMedCrossRefGoogle Scholar
  39. Kuhn KH, Haug T (1994) Ultrastructural, cytochemical, and immunocytochemical characterization of hemocytes of the hard tick Ixodes ricinus (Acari Chelicerata). Cell Tissue Res 277:493–504CrossRefGoogle Scholar
  40. Lehane MJ, Aksoy S, Levashina E (2004) Immune responses and parasite transmission in blood-feeding insects. Trends Parasitol 20:433–439PubMedCrossRefGoogle Scholar
  41. Levashina EA, Moita LF, Blandin S et al (2001) Conserved role of a complement-like protein in phagocytosis revealed by dsRNA knockout in cultured cells of the mosquito, Anopheles gambiae. Cell 104:709–718PubMedCrossRefGoogle Scholar
  42. Loosova G, Jindrak L, Kopacek P (2001) Mortality caused by experimental infection with the yeast Candida haemulonii in the adults of Ornithodoros moubata (Acarina: Argasidae). Folia Parasitol (Praha) 48:149–153Google Scholar
  43. Man P, Kovar V, Sterba J et al (2008) Deciphering Dorin M glycosylation by mass spectrometry. Eur J Mass Spectrom (Chichester, Eng) 14:345–354CrossRefGoogle Scholar
  44. Mattila JT, Munderloh UG, Kurtti TJ (2007) Phagocytosis of the Lyme disease spirochete, Borrelia burgdorferi, by cells from the ticks, Ixodes scapularis and Dermacentor andersoni, infected with an endosymbiont, Rickettsia peacockii. J Insect Sci 7(58):1–12CrossRefGoogle Scholar
  45. Moita LF, Wang-Sattler R, Michel K et al (2005) In vivo identification of novel regulators and conserved pathways of phagocytosis in A. gambiae. Immunity 23:65–73PubMedCrossRefGoogle Scholar
  46. Nava S, Guglielmone AA, Mangold AJ (2009) An overview of systematics and evolution of ticks. Front Biosci 14:2857–2877PubMedCrossRefGoogle Scholar
  47. Nene V (2009) Tick genomics–coming of age. Front Biosci 14:2666–2673PubMedCrossRefGoogle Scholar
  48. Nonaka M, Kimura A (2006) Genomic view of the evolution of the complement system. Immunogenetics 58:701–713PubMedCrossRefGoogle Scholar
  49. Osta MA, Christophides GK, Vlachou D et al (2004) Innate immunity in the malaria vector Anopheles gambiae: comparative and functional genomics. J Exp Biol 207:2551–2563PubMedCrossRefGoogle Scholar
  50. Pereira LS, Oliveira PL, Barja-Fidalgo C et al (2001) Production of reactive oxygen species by hemocytes from the cattle tick Boophilus microplus. Exp Parasitol 99:66–72PubMedCrossRefGoogle Scholar
  51. Rego RO, Hajdusek O, Kovar V et al (2005) Molecular cloning and comparative analysis of fibrinogen-related proteins from the soft tick Ornithodoros moubata and the hard tick Ixodes ricinus. Insect Biochem Mol Biol 35:991–1004PubMedCrossRefGoogle Scholar
  52. Rego RO, Kovar V, Kopacek P et al (2006) The tick plasma lectin, Dorin M, is a fibrinogen-related molecule. Insect Biochem Mol Biol 36:291–299PubMedCrossRefGoogle Scholar
  53. Ricklin D, Hajishengallis G, Yang K et al (2010) Complement: a key system for immune surveillance and homeostasis. Nat Immunol 11:785–797PubMedCrossRefGoogle Scholar
  54. Rittig MG, Kuhn KH, Dechant CA et al (1996) Phagocytes from both vertebrate and invertebrate species use “coiling” phagocytosis. Dev Comp Immunol 20:393–406PubMedCrossRefGoogle Scholar
  55. Saravanan T, Weise C, Sojka D et al (2003) Molecular cloning, structure and bait region splice variants of alpha2-macroglobulin from the soft tick Ornithodoros moubata. Insect Biochem Mol Biol 33:841–851PubMedCrossRefGoogle Scholar
  56. Sonenshine DE (1991) Biology of ticks, vol 1. Oxford University Press, New YorkGoogle Scholar
  57. Sonenshine DE, Hynes WL (2008) Molecular characterization and related aspects of the innate immune response in ticks. Front Biosci 13:7046–7063PubMedCrossRefGoogle Scholar
  58. Stroschein-Stevenson SL, Foley E, O’Farrell PH et al (2006) Identification of Drosophilagene products required for phagocytosis of Candida albicans. PLoS Biol 4:e4PubMedCrossRefGoogle Scholar
  59. Zhu Y, Thangamani S, Ho B et al (2005) The ancient origin of the complement system. EMBO J 24:382–394PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Petr Kopacek
    • 1
  • Ondrej Hajdusek
    • 1
    • 2
  • Veronika Buresova
    • 1
  1. 1.Institute of Parasitology, Biology CentreAcademy of Sciences of the Czech RepublicCeské BudejoviceCzech Republic
  2. 2.Institut de Biologie Moléculaire et Cellulaire (IBMC)Université Louis PasteurStrasbourg CedexFrance

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