Exploring the Sialomes of Ticks

  • Youmna M’ghirbiEmail author
Part of the Entomology in Focus book series (ENFO, volume 4)


Ticks (Acarina) are obligate blood-feeding arthopods that vector human and animal pathogens, causing typhus, Lyme disease, Rocky Mountain spotted fever, tick-borne relapsing fever, babesiosis, Q fever, arboviruses, anaplasmosis, and ehrlichiosis. Among the specializations required for this peculiar diet, tick saliva, a fluid once believed to be relevant only for lubrication of mouthparts and water balance, is now well known to be a cocktail of potent antihemostatic, anti-inflammatory, and immunomodulatory molecules that helps these arthropods obtain a blood meal from their vertebrate hosts. The repertoire of pharmacologically active components in this cocktail is impressive as well as the number of targets they specifically affect. These salivary components change the physiology of the host at the bite site, and, consequently, some pathogens transmitted by ticks take advantage of this change and become more infective. Tick salivary proteins have therefore become an attractive target to control tick-borne diseases. Recent advances in molecular biology, protein chemistry, and computational biology are accelerating the isolation, sequencing, and analysis of a large number of transcripts and proteins from the saliva of different ticks. Many of these newly isolated genes code for proteins with homology to known proteins allowing identification or prediction of their function. These and other molecules from genome and proteome sequences offer an exciting possibility to identify new vaccine antigens, potential biopharmaceuticals, antimicrobial peptides, and other novel human therapeutics.


Sialomes Ticks Acarina Sialotranscriptome Sialoproteome Pharmacologically active components 



Adenosine diphosphate


Activated partial thromboplastin time


Adenosine triphosphate


B-cell inhibitory proteins


Boophilus microplus anticoagulant protein


Rhipicephalus microplus trypsin inhibitor-A


Basic protease inhibitor–Kunitz type


Cyclic adenosine monophosphate


Dendritic cell


Extracellular matrix


Extrinsic tenase complex


Factor IXa


Factor VIII


Factor X


Factor Xa


Glycoprotein IIb–IIIa


The concentration of an inhibitor where the response (or binding) is reduced by half






Ixodes ricinus contact phase inhibitor


I. ricinus serine proteinase inhibitor (serpin)


I. scapularis anticomplement


Ixodes scapularis salivary proteins


Macrophage migration inhibitory factor


National Center for Biotechnology Information


Natural killer


Ornithodoros moubata complement inhibitor


Prostaglandin E2


Prostaglandin F2


Prothrombin time


Rhipicephalus appendiculatus histamine-binding salivary protein


Salivary protein


Saliva-assisted transmission


Salivary gland


Salivary gland extract


serotonin- and histamine- binding protein


Tick adhesion inhibitor


Tick anticoagulant peptide


Tick-derived protease inhibitor


Tissue factor


Tick histamine release factor


Thrombin time


  1. 1.
    Jongejan, F., & Uilenberg, G. (2004). The global importance of ticks. Parasitology, 129, S3–S14.PubMedCrossRefGoogle Scholar
  2. 2.
    Ribeiro, J. M. C. (1987). Role of saliva in blood-feeding by arthropods. Annual Review of Entomology, 32, 463–478.PubMedCrossRefGoogle Scholar
  3. 3.
    Ribeiro, J. M. C. (1995). Blood-feeding arthropods: Live syringes or invertebrate pharmacologists? Infectious Agents and Disease, 4, 143–152.PubMedGoogle Scholar
  4. 4.
    Wikel, S. K. (1999). Tick modulation of host immunity: An important factor in pathogen transmission. International Journal of Parasitology, 28, 851–859.CrossRefGoogle Scholar
  5. 5.
    Gillespie, R. D., Mbow, M. L., & Titus, R. G. (2000). The immunomodulatory factors of blood feeding arthropods saliva. Parasite Immunology, 22, 319–331.PubMedCrossRefGoogle Scholar
  6. 6.
    Valenzuela, J. G., Charlab, R., Mather, T. N., & Ribeiro, J. M. C. (2000). Purification, cloning and expression of a novel salivary anti-complement protein from the tick, Ixodes scapularis. Journal of Biological Chemistry, 275, 18717–18723.PubMedCrossRefGoogle Scholar
  7. 7.
    Francischetti, I. M., Sa-Nunes, A., Mans, B. J., Santos, I. M., & Ribeiro, J. M. (2009). The role of saliva in tick feeding. Frontiers in Bioscience, 14, 2051–2088.CrossRefGoogle Scholar
  8. 8.
    Chmelar, J., Calvo, E., Pedra, J. H. F., Francischetti, I. M., & Kotsyfakis, M. (2012). Tick salivary secretion as a source of anti-hemostatics. Journal of Proteomics, 75, 3842–3854.PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Randolph, S. E. (2009). Tick-borne disease systems emerge from the shadows: The beauty lies in molecular detail, the message in epidemiology. Parasitology, 136, 1403–1413.PubMedCrossRefGoogle Scholar
  10. 10.
    Nuttall, P. A., & Labuda, M. (2004). Tick-host interactions: Saliva-activated transmission. Parasitology, 129, S177–S189.PubMedCrossRefGoogle Scholar
  11. 11.
    Kazimírová, M., & Štibrániová, I. (2013). Tick salivary compounds: Their role in modulation of host defenses and pathogen transmission. Cellular and Infection Microbiology, 43, 1–19.Google Scholar
  12. 12.
    Ribeiro, J. M. C. (1989). Role of saliva in tick/host interactions. Experimental and Applied Acarology, 7, 15–20.PubMedCrossRefGoogle Scholar
  13. 13.
    Maritz-Olivier, C., Christian Stutzer, C., Jongejan, F., Neitz, A. W. H., & Gaspar, A. R. M. (2007). Tick anti-hemostatics: Targets for future vaccines and therapeutics. Trends in Parasitology, 23, 397–407.PubMedCrossRefGoogle Scholar
  14. 14.
    Karim, S., Singh, P., & Ribeiro, J. M. (2011). A deep insight into the sialotranscriptome of the gulf coast tick, Amblyomma maculatum. PLoS ONE, 6(12), e28525.PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Ribeiro, J. M., Anderson, J. M., Manoukis, N. C., Meng, Z., & Francischetti, I. M. (2011). A further insight into the sialome of the tropical bont tick, Amblyomma variegatum. BMC Genomics, 12, 136–147.PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Valenzuela, J. G. (2004). Exploring tick saliva: From biochemistry to “sialomes” and functional genomics. Parasitology, 129, S83–S94.PubMedCrossRefGoogle Scholar
  17. 17.
    Arocha-Piñango, C. L., Marchi, R., Carvajal, Z., & Guerrero, B. (1999). Invertebrate compounds acting on the hemostatic mechanism. Blood Coagulation and Fibrinolysis, 10, 43–68.PubMedCrossRefGoogle Scholar
  18. 18.
    Kazimírová, M. (2007). Chapter VIII. Bioactive compounds in ticks acting on host thrombohemostasis. In V. Wiwanitkit (Ed.), Thrombohemostatic disease research (pp. 95–113). New York: Nova Science Publishers, Inc.Google Scholar
  19. 19.
    Mans, B. J., Andersen, J. F., Francischetti, I. M. B., Valenzuela, J. G., Schwan, T. G., Pham, V. M., Garfield, M. K., Hammer, C. H., & Ribeiro, J. M. C. (2008). Comparative sialomics between hard and soft ticks: Implications for the evolution of blood-feeding behavior. Insect Biochemisry and Molecular Biology, 38, 42–58.CrossRefGoogle Scholar
  20. 20.
    Ribeiro, J. M. C., Makoul, G. T., & Robinson, D. R. (1988). Ixodes dammini: Evidence for salivary prostacyclin secretion. Journal of Parasitology, 74, 1068–1069.PubMedCrossRefGoogle Scholar
  21. 21.
    Dai, J., Narasimhan, S. Z., Liu, L., Wang, P., & Fikrig, E. (2010). Tick histamine release factor is critical for Ixodes scapularis engorgement and transmission of the Lyme disease agent. PLoS Pathogen, 6, e1001205. doi: 10.1371/journal.ppat.1001205.CrossRefGoogle Scholar
  22. 22.
    Chmelar, J., Oliveira, C. J., Rezacova, P., Francischetti, I. M., Kovarova, Z., Pejler, G., et al. (2011). A tick salivary protein targets cathepsin G and chymase and inhibits host inflammation and platelet aggregation. Blood, 117, 736–744.PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Ribeiro, J. M. C., Evans, P. M., MacSwain, J. L., & Sauer, J. (1992). Amblyomma americanum: Characterization of salivary prostaglandins E2 and F2 alpha by RP-PLC/bioassay and gas chromatography-mass spectrometry. Experimental Parasitology, 74, 112–116.PubMedCrossRefGoogle Scholar
  24. 24.
    Aljamali, M., Bowman, A. S., Dillwith, J. W., Tucker, J. S., Yates, G. W., Essenberg, R. C., & Sauer, J. R. (2002). Identity and synthesis of prostaglandins in the lone star tick, Amblyomma americanum (L.), as assessed by radio-immunoassay and gas chromatography/mass spectrometry. Insect Biochemisry and Molecular Biology, 32, 331–341.CrossRefGoogle Scholar
  25. 25.
    Dickinson, R. G., O’hagan, J. E., Shotz, M., Binnington, K. C., & Hegarty, M. P. (1976). Prostaglandin in the saliva of the cattle tick Boophilus microplus. Australian Journal of Experimental Biology & Medical Science, 54, 475–486.CrossRefGoogle Scholar
  26. 26.
    Mans, B. J., Louw, A. I., Gaspar, A. R. M. D., & Neitz, A. W. H. (1998). Purification and characterization of apyrase from the tick, Ornithodoros savignyi. Comparative Biochemistry and Physiology. Part B, Biochemistry and Molecular Biology, 120, 617–624.PubMedCrossRefGoogle Scholar
  27. 27.
    Schuijt, T. J., Bakhtiari, K., Daffre, S., Deponte, K., Wielders, S. J., Marquart, J. A., et al. (2013). Factor Xa activation of factor V is of paramount importance in initiating the coagulation system: Lessons from a tick salivary protein. Circulation, 128, 254–266.PubMedCrossRefGoogle Scholar
  28. 28.
    Waxman, L., & Connolly, T. M. (1993). Isolation of an inhibitor selective for collagen-stimulated platelet aggregation from the soft tick Ornithodoros moubata. Journal of Biological Chemistry, 268, 5445–5449.PubMedGoogle Scholar
  29. 29.
    Karczewski, J., Endris, R., & Connolly, T. M. (1994). Disagregin is a fibrinogen receptor antagonist lacking the Arg-Gly-Asp sequence from the tick, Ornithodoros moubata. Journal of Biological Chemistry, 269, 6702–6708.PubMedGoogle Scholar
  30. 30.
    Man, B. J., Louw, A. I., & Neitz, A. W. H. (2002). Savignygrin, a platelet aggregation inhibits or from the soft tick Ornithodoros savignyi, present the RGD integrin recognition motif on the Kunitz-BPTI fold. Journal of Biological Chemistry, 277, 21371–21378.CrossRefGoogle Scholar
  31. 31.
    Mans, B. J., Louw, A. I., & Neitz, A. W. H. (2002). Evolution of hematophagy in ticks: Common origins for blood coagulation and platelet aggregation inhibitors from soft ticks of the genus Ornithodoros. Molecular Biology and Evolution, 19, 1695–1705.PubMedCrossRefGoogle Scholar
  32. 32.
    Nienaber, J., Gaspar, A. R. M., & Neitz, A. W. H. (1999). Savignin, a potent thrombin inhibitor isolated from the salivary glands of the tick Ornithodoros savignyi (Acari: Argasidae). Experimental Parasitology, 93, 82–91.PubMedCrossRefGoogle Scholar
  33. 33.
    Ribeiro, J. M. C., Endris, T. M., & Endris, R. (1991). Saliva of the soft tick, Ornithodoros moubata, contains anti-platelet and apyrase activities. Comparative Biochemistry and Physiology Part A, 100, 109–112.CrossRefGoogle Scholar
  34. 34.
    Keller, P. M., Waxman, L., Arnold, B. A., Schultz, L. D., Condra, C., & Connolly, T. M. (1993). Cloning of the cDNA and expression of moubatin, an inhibitor of platelet aggregation. Journal of Biological Chemistry, 268, 5450–5456.PubMedGoogle Scholar
  35. 35.
    Karczewski, J., Waxman, L., Endris, R. G., & Connolly, T. M. (1995). An inhibitor from the argasid tick Ornithodoros moubata of cell adhesion to collagen. Biochemical and Biophysical Research Communications, 208, 532–541.PubMedCrossRefGoogle Scholar
  36. 36.
    Ribeiro, J. M. C., Makoul, G. T., Robinson, D. R., & Spielman, A. (1985). Antihemostatic, anti-inflammatory, and immunosuppressive properties of the saliva of a tick, Ixodes dammini. Journal of Experimental Medicine, 161, 332–344.PubMedCrossRefGoogle Scholar
  37. 37.
    Francischetti, I. M. B., Pham, V. M., Mans, B. J., Andersen, J. F., Mather, T. N., Lane, R. S., et al. (2005). The transcript-tome of the salivary glands of the female western black-legged tick Ixodes pacificus (Acari: Ixodidae). Insect Biochemistry and Molecular Biology, 35, 1142–1161.PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Cheng, Y., Wu, H., & Li, D. (1999). An inhibitor selective for collagen-stimulated platelet aggregation from the salivary glands of hard tick Haemaphysalis longicornis and its mechanism of action. Science in China. Series C, Life Sciences, 42, 457–464.PubMedCrossRefGoogle Scholar
  39. 39.
    Wang, X., Coons, L. B., Taylor, D. B., Stevens, S. E., & Gartner, T. K. (1996). Variabilin, a novel RGD-containing antagonist of glycoprotein IIb-IIIa and platelet aggregation inhibit or from the hard tick Dermacentor variabilis. Journal of Biological Chemistry, 271, 17785–17790.PubMedCrossRefGoogle Scholar
  40. 40.
    Iwanaga, S., Okada, M., Isawa, H., Morita, A., Yuda, M., & Chinzei, Y. (2003). Identification and characterization of novel salivary thrombin inhibitors from the ixodidae tick, Haemaphysalis longicornis. European Journal of Biochemistry, 270, 1926–1934.PubMedCrossRefGoogle Scholar
  41. 41.
    Zhu, K., Sauer, J. R., Bowman, A. S., & Dillwith, J. W. (1997). Identification and characterization of anticoagulant activities in the saliva of the lone star tick, Amblyomma americanum (L). Journal of Parasitology, 83, 38–43.PubMedCrossRefGoogle Scholar
  42. 42.
    Horn, F., Coutinhodos Carlos, P., & Termignoni, C. (2000). Boophilus microplus anti-coagulant protein: An anti-thrombin inhibitor isolated from the cattle tick saliva. Archives of Biochemistry and Biophysics, 384, 68–73.PubMedCrossRefGoogle Scholar
  43. 43.
    Waxman, L., Smith, D. E., Arcuri, K. E., & Vlasuk, G. P. (1990). Tick Anti-coagulant Peptide (TAP) is a novel inhibitor of blood coagulation factor Xa. Science, 248, 593–596.PubMedCrossRefGoogle Scholar
  44. 44.
    Van de Locht, A., Stubbs, M. T., Bode, W., Friedrich, T., Bollschweiler, C., Hoffken, W., et al. (1996). The ornithodorin-thrombin crystal structure a key to the TAP enigma. EMBO Journal, 15, 6011–6017.PubMedPubMedCentralGoogle Scholar
  45. 45.
    Joubert, A. M., Louw, A. I., Joubert, F., & Neitz, A. W. H. (1998). Cloning nucleotide sequence and expression of the gene encoding factor Xa inhibitor from the salivary glands of the tick, Ornithodoros savignyi. Experimental and Applied Acarology, 22, 603–619.PubMedCrossRefGoogle Scholar
  46. 46.
    Ehebauer, M. T., Mans, B. J., Gaspar, A. R. M., & Neitz, A. W. H. (2002). Identification of extrinsic blood coagulation pathway inhibitors from the tick Ornithodoros savignyi (Acari: Argasidae). Experimental Parasitology, 101, 138–148.PubMedCrossRefGoogle Scholar
  47. 47.
    Francischetti, I. M. B., Valenzuela, J. G., Andersen, J. F., Mather, T. N., & Ribeiro, J. M. C. (2002). Ixolaris, a novel recombinant tissue factor pathway inhibitor (TFPI) from the salivary gland of the tick, Ixodes scapularis: identification of factor X and factor Xa as scaffolds for the inhibition of factor VIIa/Tissue factor complex. Hemost. Thromb. Vascular Biology, 99, 3602–3612.Google Scholar
  48. 48.
    Narasimhan, S., Koski, R. A., Beaulieu, B., Anderson, J. F., Ramamoorthi, N., Kantor, F., et al. (2002). A novel family of anticoagulants from the saliva of Ixodes scapularis. Insect Molecular Biology, 11, 641–650.PubMedCrossRefGoogle Scholar
  49. 49.
    Nunn, M. A., Sharma, A., Paesen, G. C., Adamson, S., Lissina, O., Willis, A. C., et al. (2005). Complement inhibitor of C5 activation from the soft tick Ornithodoros moubata. Journal of Immunology, 174, 2084–2091.CrossRefGoogle Scholar
  50. 50.
    Decrem, Y., Rath, G., Blasioli, V., Cauchie, P., Robert, S., Beaufays, J., et al. (2009). Ir-CPI, a coagulation contact phase inhibitor from the tick Ixodes ricinus, inhibits thrombus formation without impairing hemostasis. Journal of Experimental Medicine, 206, 2381–2395.PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Koh, C. Y., Kazimirova, M., Trimnell, A., Takac, P., Labuda, M., Nuttall, P. A., et al. (2007). Variegin a novel fast and tight binding thrombin inhibitor from the tropical bont tick. Journal of Biological Chemistry, 282, 29101–29113.PubMedCrossRefGoogle Scholar
  52. 52.
    Zhu, K., Bowman, A. S., Brigham, D. L., Essenberg, R. C., Dillwith, J. W., & Sauer, J. R. (1997). Isolation and characterization of americanin, a specific inhibitor of thrombin, from the salivary glands of the lone star tick Amblyomma americanum (L.). Experimental Parasitology, 87, 30–38.PubMedCrossRefGoogle Scholar
  53. 53.
    Batista, I. F. C., Ramos, O. H. P., Ventura, J. S., Junqueira-de- Azevedo, I. L. M., Ho, P. L., & Chudzinski-Tavassi, A. M. (2010). A new Factor Xa inhibitor from Amblyomma cajennense with a unique domain composition. Archives of Biochemistry and Biophysics, 493, 151–156.PubMedCrossRefGoogle Scholar
  54. 54.
    Kato, N., Iwananga, S., Okayama, T., Isawa, H., Yuda, M., & Chinzei, Y. (2005). Identification and characterization of the plasma kallikrein-kinin system inhibitor, haemaphysalin, from hard tick, Haemaphysalis longicornis. Thrombosis and Haemostasis, 93, 359–367.PubMedGoogle Scholar
  55. 55.
    Avraamides, C. J., Garmy-Susini, B., & Varner, J. A. (2008). Integrins in angiogenesis and lymphangiogenesis. Nature Reviews Cancer, 8, 604–617.PubMedPubMedCentralCrossRefGoogle Scholar
  56. 56.
    Limo, M. K., Voigt, W. P., Tumbo-Oeri, A., Njogu, R. M., & Ole-Moi Yoi, O. N. (1991). Purification and characterization of an anticoagulant from the salivary glands of the ixodid tick Rhipicephalus appendiculatus. Experimental Parasitology, 72, 418–429.PubMedCrossRefGoogle Scholar
  57. 57.
    Macedo-Ribeiro, S., Almeida, C., Calisto, B. M., Friedrich, T., Mentele, R., Stürzebecher, J., et al. (2008). Isolation, cloning and structural characterization of boophilin, a multifunctional Kunitz-type proteinase inhibitor from the cattle tick. PLoS ONE, 3, e1624.PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Ciprandi, A., de Oliveira, S. K., Masuda, A., Horn, F., & Termignoni, C. (2006). Boophilus microplus: Its saliva contains microphilin, a small thrombin inhibitor. Experimental Parasitology, 114, 40–46.PubMedCrossRefGoogle Scholar
  59. 59.
    Motoyashiki, T., Tu, A. T., Ayimov, D. A., & Ibragim, K. (2003). Isolation of anti-coagulant from the venom of tick, Boophilus calcaratus, from Uzbekistan. Thrombosis Research, 110, 235–241.PubMedCrossRefGoogle Scholar
  60. 60.
    Gordon, J. R., & Allen, J. R. (1991). Factors V and VII anticoagulant activities in the salivary glands of feeding Dermacentor andersoni ticks. Journal of Parasitology, 77, 167–170.PubMedCrossRefGoogle Scholar
  61. 61.
    Joubert, A. M., Crause, J. C., Gaspar, A. R., Clarke, F. C., Spickett, M., & Neitz, A. W. (1995). Isolation and characterization of an anticoagulant present in the salivary glands of the bont-legged tick, Hyalomma truncatum. Experimental and Applied Acarology, 19, 79–92.PubMedCrossRefGoogle Scholar
  62. 62.
    Tyson, K., Elkins, C., Patterson, H., Fikrig, E., & deSilva, A. (2007). Biochemical and functional characterization of Salp20, an Ixodes scapularis tick salivary protein that inhibits the complement pathway. Insect Molecular Biology, 16, 469–479.PubMedCrossRefGoogle Scholar
  63. 63.
    Guo, X., Booth, C. J., Paley, M. A., Wang, X., DePonte, K., Fikrig, E., Narasimhan, S., & Montgomery, R. R. (2009). Inhibition of neutrophil function by two tick salivary proteins. Infection and Immunity, 77, 2320–2329.PubMedPubMedCentralCrossRefGoogle Scholar
  64. 64.
    Hannier, S., Liversidge, J., Sternberg, J. M., & Bowman, A. S. (2004). Characterization of the B-cell inhibitory protein factor in Ixodes ricinus tick saliva: A potential role in enhanced Borrelia burgdorferi transmission. Immunology, 113, 401–408.PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Mans, B. J., Louw, A. I., Gaspar, A. R. M. D., & Neitz, A. W. H. (1998). Apyrase activity and platelet aggregation inhibitors in the tick Ornithodoros savignyi. Experimental and Applied Acarology, 22, 353–366.PubMedCrossRefGoogle Scholar
  66. 66.
    Kotsyfakis, M., Sa-Nunes, A., Francischetti, I. M., Mather, T. N., Andersen, J. F., & Ribeiro, J. M. C. (2006). Anti-inflammatory and immune suppressive activity of sialostatin L, a salivary cystatin from the tick Ixodes scapularis. Journal of Biological Chemistry, 281, 26298–26307.PubMedCrossRefGoogle Scholar
  67. 67.
    Prevot, P. P., Adam, B., Boudjeltia, K. Z., Brossard, M., Lins, L., Cauchie, P., et al. (2006). Anti-hemostatic effects of a serpin from the saliva of the tick Ixodes ricinus. Journal of Biological Chemistry, 281, 26361–26369.PubMedCrossRefGoogle Scholar
  68. 68.
    Yu, D., Liang, J., Yu, H., Wu, H., Xu, C., Liu, J., et al. (2006). A tick B-cell inhibitory protein from salivary glands of the hard tick, Hyalomma asiaticum asiaticum. Biochemical and Biophysical Research Communications, 343, 585–590.PubMedCrossRefGoogle Scholar
  69. 69.
    Brossard, M., & Wikel, S. K. (2008). Tick immune biology. In A. S. Bowman & P. A. Nuttall (Eds.), Ticks: Biology, disease and control (pp. 186–204). Cambridge/New York: Cambridge University Press.CrossRefGoogle Scholar
  70. 70.
    Beaufays, J., Adam, B., Menten-Dedoyart, C., Fievez, L., Grosjean, A., Decrem, Y., et al. (2008). Ir-LBP, an Ixodes ricinus tick salivary LTB4-bindinglipocalin, interferes with host neutrophil function. PLoS ONE, 3, e3987.PubMedPubMedCentralCrossRefGoogle Scholar
  71. 71.
    Frauenschuh, A., Power, C. A., Déruaz, M., Ferreira, B. R., DaSilva, J., Teixeira, M. M., et al. (2007). Molecular cloning and characterization of a highly selective chemokine-binding protein from the tick Rhipicephalus sanguineus. Journal of Biological Chemistry, 282, 27250–27258.PubMedCrossRefGoogle Scholar
  72. 72.
    Wu, J., Wang, Y., Liu, H., Yang, H., Ma, D., Li, J., et al. (2010). Two immune regulatory pep-tides with antioxidant activity from tick salivary glands. Journal of Biological Chemistry, 285, 16606–16613.PubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    Jaworski, D. C., Jasinskas, A., Metz, C. N., Bucala, R., & Barbour, A. G. (2001). Identification and characterization of a homologue of the pro-inflammatory cytokine, macrophage migration inhibitory factor in the tick, Amblyomma americanum. Insect Molecular Biology, 10, 323–331.PubMedCrossRefGoogle Scholar
  74. 74.
    Wang, H., & Nuttall, P. A. (1999). Immunoglobulin-binding proteins in ticks: New target for vaccine development against a blood- feeding parasite. Cellular and Molecular Life Sciences, 56, 286–295.PubMedCrossRefGoogle Scholar
  75. 75.
    Preston, S. G., Majtán, J., Kouremenou, C., Rysnik, O., Burger, L. F., Cabezas Cruz, A., et al. (2013). Novel immune modulators from hard ticks selectively reprogramme human dendritic cell responses. PLoS Pathogen, 9, e1003450.CrossRefGoogle Scholar
  76. 76.
    Oliveira, C. J., Sa-Nunes, A., Francischetti, I. M., Carregaro, V., Anatriello, E., Silva, J. S., et al. (2011). Deconstructing tick saliva: Non-protein molecules with potent immune modulatory properties. Journal of Biological Chemistry, 286, 10960–10969.PubMedPubMedCentralCrossRefGoogle Scholar
  77. 77.
    Ribeiro, J. M. C. (1987). Ixodes dammini: Salivary anti-complement activity. Experimental Parasitology, 64, 347–353.PubMedCrossRefGoogle Scholar
  78. 78.
    Paesen, G. C., Adams, P. L., Harlos, K., Nuttall, P. A., & Stuart, D. I. (1999). Tick histamine-binding proteins: Isolation, cloning and three dimensional structure. Molecular Cell, 3, 661–671.PubMedCrossRefGoogle Scholar
  79. 79.
    Couvreur, B., Beaufays, J., Charon, C., Lahaye, K., Gensale, F., Denis, V., et al. (2008). Variability and action mechanism of a family of anti-complement proteins in Ixodes ricinus. PLoS ONE, 3, e1400.PubMedPubMedCentralCrossRefGoogle Scholar
  80. 80.
    Anguita, J., Ramamoorthi, N., Hovius, J. W., Das, S., Thomas, V., Persinski, R., et al. (2002). Salp15, an Ixodes scapularis salivary protein, inhibits CD4(+) T cell activation. Immunity, 16, 849–859.PubMedCrossRefGoogle Scholar
  81. 81.
    Déruaz, M., Frauenschuh, A., Alessandri, A. L., Dias, J. M., Coelho, F. M., Russo, R. C., et al. (2008). Ticks produce highly selective chemokine binding proteins with anti-inflammatory activity. Journal of Experimental Medicine, 205, 2019–2031.PubMedPubMedCentralCrossRefGoogle Scholar
  82. 82.
    Kubeš, M., Fuchsberger, N., Labuda, M., Žuffová, E., & Nuttall, P. A. (1994). Salivary gland extracts of partially fed Dermacentor reticulatus ticks decrease natural killer cell activity in vitro. Immunology, 82, 113–116.PubMedPubMedCentralGoogle Scholar
  83. 83.
    Decrem, Y., Beaufays, J., Blasioli, V., Lahaye, K., Brossard, M., Vanhamme, L., et al. (2008). A family of putative metalloproteases in the salivary glands of the tick Ixodes ricinus. FEBS Journal, 275, 1485–1499.PubMedCrossRefGoogle Scholar
  84. 84.
    Islam, M. K., Tsuji, N., Miyoshi, T., Alim, M. A., Huang, X., Hatta, T., et al. (2009). The Kunitz-like modulatory protein haemangin is vital for hard tick blood-feeding success. PLoS Pathogen, 5, e1000497.CrossRefGoogle Scholar
  85. 85.
    Fukumoto, S., Sakaguchi, T., You, M., Xuan, X., & Fujisaki, K. (2006). Tick troponin I-like molecule is a potent inhibitor for angiogenesis. Microvascular Research, 71, 218–221.PubMedCrossRefGoogle Scholar
  86. 86.
    Karczewski, J., & Connolly, T. M. (1997). The interaction of disagregin with the platelet fibrinogen receptor, glycoprotein IIb-IIIa. Biochemical and Biophysical Research Communications, 241, 744–748.PubMedCrossRefGoogle Scholar
  87. 87.
    Bowman, A. S., Dillwith, J. W., & Sauer, J. R. (1996). Tick salivary prostaglandins: Presence, origin, and significance. Parasitology Today, 12, 388–396.PubMedCrossRefGoogle Scholar
  88. 88.
    Inokuma, H., Kemp, D. H., & Willadsen, P. (1994). Prostaglandin E2 production by the cattle tick (Boophilus microplus) into feeding sites and its effect on the response of bovine mononuclear cells to mitogen. Veterinary Parasitology, 53, 293–299.PubMedCrossRefGoogle Scholar
  89. 89.
    Francischetti, I. M. B. (2010). Platelet aggregation inhibitors from hematophagous animals. Toxicon, 56, 1130–1144.PubMedCrossRefGoogle Scholar
  90. 90.
    Ferguson, J. J., & Zaqqa, M. (1999). Platelet glycoprotein IIb/IIIa receptor antagonists: Current concepts and future directions. Drugs, 58, 965–982.PubMedCrossRefGoogle Scholar
  91. 91.
    Mans, B. J., Louw, A. I., & Neitz, A. W. (2003). The major tick salivary gland proteins and toxins from the soft tick, Ornithodoros savignyi are part of the tick lipocalin family: Implications for the origins of tick toxicoses. Molecular Biology and Evolution, 20, 1158–1167.PubMedCrossRefGoogle Scholar
  92. 92.
    Mans, B. J., Coetzee, J., Louw, A. I., Gaspar, A. R. M., & Neitz, A. W. H. (2000). Disaggregation of aggregated platelets by apyrase from the tick Ornithodoros savignyi (Acari: Argasidae). Experimental and Applied Acarology, 24, 271–282.PubMedCrossRefGoogle Scholar
  93. 93.
    Liyou, N., Hamilton, S., Elvin, C., & Willadsen, P. (1999). Cloning, expression of ecto 5′-nucleotidase from cattle tick Boophilus microplus. Insect Molecular Biology, 8, 257–266.PubMedCrossRefGoogle Scholar
  94. 94.
    Bowman, A. S., Sauer, J. R., Zhu, K., & Dillwith, J. W. (1995). Biosynthesis of salivary prostaglandins in the lone star tick, Amblyomma americanum. Insect Biochemisry and Molecular Biology, 25, 735–741.CrossRefGoogle Scholar
  95. 95.
    Hoffmann, A., Walsmann, P., Riesener, G., Paintz, M., & Markwardt, F. (1991). Isolation and characterization of a thrombin inhibitor from the tick Ixodes ricinus. Pharmazie, 46, 209–212.PubMedGoogle Scholar
  96. 96.
    Koh, C. Y., & Kini, R. M. (2009). Molecular diversity of anticoagulants from haematophagous animals. Thrombosis and Haemostasis, 102, 437–453.PubMedGoogle Scholar
  97. 97.
    Gao, X., Shi, L., Zhou, Y., Cao, J., Zhang, H., & Zhou, J. (2011). Characterization of the anti-coagulant protein Rhipilin-1 from the Rhipicephalus haemaphysaloides tick. Journal of Insect Physiology, 57, 339–343.PubMedCrossRefGoogle Scholar
  98. 98.
    Narasimhan, S., Montgomery, R. R., DePonte, K., Tschudi, C., Marcantonio, N., Anderson, J. F., et al. (2004). Disruption of Ixodes scapularis anticoagulation by using RNA interference. Proceedings of the National Academy of Sciences of the United States of America, 101, 1141–1146.PubMedPubMedCentralCrossRefGoogle Scholar
  99. 99.
    Francischetti, I. M. B., Mather, T. N., & Ribeiro, J. M. C. (2004). Penthalaris a novel recombinant five-Kunitz tissue factor pathway inhibitor (TFPI) from the salivary gland of the tick vector of Lyme disease, Ixodes scapularis. Thrombosis and Haemostasis, 91, 886–898.PubMedGoogle Scholar
  100. 100.
    Tanaka, A. S., Andreotti, R., Gomes, A., Torquato, R. J. S., Sampaio, M. U., & Sampaio, C. A. M. (1999). A Double-headed serine protease inhibitor—Human plasma kallikrein and elastase inhibitor— From Boophilus microplus larvae. Immunopharmacology, 45, 171–177.PubMedCrossRefGoogle Scholar
  101. 101.
    Francischetti, I. M. B., Mather, T. N., & Ribeiro, J. M. C. (2003). Cloning of a salivary gland metalloprotease and characterization of gelatinase and fibrin(ogen)lytic activities in the saliva of the Lyme disease tick vector Ixodes scapularis. Biochemical and Biophysical Research Communications, 305, 869–875.PubMedPubMedCentralCrossRefGoogle Scholar
  102. 102.
    Sant Anna Azzolini, S., Sasaki, S. D., Torquato, R. J., Andreotti, R., Andreotti, E., & Tanaka, A. S. (2003). Rhipicephalus sanguineus trypsin inhibitors present in the tick larvae: Isolation, characterization, and partial primary structure determination. Archives of Biochemistry and Biophysics, 417, 176–182.CrossRefGoogle Scholar
  103. 103.
    Mulenga, A., Sugino, M., Nakajima, M., Sugimoto, C., & Onuma, M. (2001). Tick-encoded serine proteinase inhibitors (serpins); potential target antigens for tick vaccine development. Journal of Veterinary Medical Science, 63, 1063–1069.CrossRefGoogle Scholar
  104. 104.
    Mulenga, A., Tsuda, A., Onuma, M., & Sugimoto, C. (2003). Four serine proteinase inhibitors (serpin) from the brown ear tick, Rhipicephalus appendiculatus; cDNA cloning and preliminary characterization. Insect Biochemisry and Molecular Biology, 33, 267–276.CrossRefGoogle Scholar
  105. 105.
    Jaworski, D. C., Simmen, F. A., Lamoreaux, W., Coons, L. B., Muller, M. T., & Needham, G. R. (1995). A secreted calreticulin protein in ixodid tick (Amblyomma americanum) saliva. Journal of Insect Physiology, 41, 369–375.CrossRefGoogle Scholar
  106. 106.
    Bowman, A. S., Gengler, C. L., Surdick, M. R., Zhu, K., Essenberg, R. C., Sauer, J. R., et al. (1997). A novel phospholipase A2 activity in saliva of the lone star tick, Amblyomma americanum (L.). Experimental Parasitology, 87, 121–132.PubMedCrossRefGoogle Scholar
  107. 107.
    Zhu, K., Dillwith, J. W., Bowman, A. S., & Sauer, J. R. (1997). Identification of hemolytic activity in saliva of the lone star tick (Acari: Ixodidae). Journal of Medical Entomology, 34, 160–166.PubMedCrossRefGoogle Scholar
  108. 108.
    Ribeiro, J. M. C., Weis, J. J., & Telford, S. R. (1990). Saliva of the tick Ixodes dammini inhibits neutrophil functions. Experimental Parasitology, 70, 382–388.PubMedCrossRefGoogle Scholar
  109. 109.
    Hajnická, V., Kocáková, P., Sláviková, M., Slovák, M., Gašperík, J., Fuchsberger, N., et al. (2001). Anti-interleukin-8 activity of tick salivary gland extracts. Parasite Immunology, 23, 483–489.PubMedCrossRefGoogle Scholar
  110. 110.
    Jutel, M., Watanabe, T., Klunker, S., Akdis, M., Thomet, O. A., Malolepszy, J., Zak-Nejmark, T., Koga, R., Kobayashi, T., Blaser, K., & Akdis, C. A. (2001). Histamine regulates T-cell and antibody responses by differential expression of H1 and H2 receptors. Nature, 413, 420–425.PubMedCrossRefGoogle Scholar
  111. 111.
    Valenzuela, J. G., Francischetti, I. M. B., Pham, V. M., Garfield, M. K., Mather, T. N., & Ribeiro, J. M. C. (2002). Exploring the sialome of the tick Ixodes scapularis. Journal of Experimental Biology, 205, 2843–2864.PubMedGoogle Scholar
  112. 112.
    Aljamali, M. N., Bior, A. D., Sauer, J. R., & Essenberg, R. C. (2003). RNA interference in ticks: A study using histamine binding protein dsRNA in the female tick Amblyomma americanum. Insect Molecular Biology, 12, 299–305.PubMedCrossRefGoogle Scholar
  113. 113.
    Anisuzzaman Islam, M. K., Alim, M. A., Miyoshi, T., Hatta, T., Yamajim, K., et al. (2011). Longistatin, a plasminogen activator, is key to the availability of blood-meals for ixodid ticks. PLoS Pathogen, 7, e1001312.CrossRefGoogle Scholar
  114. 114.
    Francischetti, I. M., Mather, T. N., & Ribeiro, J. M. (2005). Tick saliva is a potent inhibitor of endothelial cell proliferation and angiogenesis. Thrombosis and Haemostasis, 94, 167–174.PubMedPubMedCentralGoogle Scholar
  115. 115.
    Teresa, C. F., Assumpcao, J. M. C., Ribeiro, J. M., Ivo, M. B., & Francischetti, I. M. (2012). Disintegrins from hematophagous sources. Toxins, 4, 296–322.CrossRefGoogle Scholar
  116. 116.
    Walsh, E. M., & Marcinkiewicz, C. (2011). Non-RGD-containing snake venom disintegrins, functional and structural relations. Toxicon, 58, 355–362.PubMedCrossRefGoogle Scholar
  117. 117.
    Francischetti, I. M., Meng, Z., Mans, B. J., Gudderra, N., Hall, M., Veenstra, T. D., Pham, V. M., Kotsyfakis, M., & Ribeiro, J. M. (2008). An insight into the salivary transcriptome and proteome of the soft tick and vector of epizootic bovine abortion, Ornithodoros coriaceus. Journal of Proteomics, 71, 493–512.PubMedPubMedCentralCrossRefGoogle Scholar
  118. 118.
    Pechová, J., Štépánová, G., Kovár, L., & Kopecký, J. (2002). Tick salivary gland extract-activated transmission of Borrelia afzelii spirochaetes. Folia Parasitologica, 49, 153–159.PubMedCrossRefGoogle Scholar
  119. 119.
    Willadsen, P., Riding, G. A., McKenna, R. V., Kemp, D. H., Tellam, R. L., Nielsen, J. N., Lahnstein, J., Cobon, G. S., & Gough, J. M. (1989). Immunologic control of a parasitic arthropod. Identification of a protective antigen from Boophilus Microplus. Journal of Immunology, 143, 1346–1351.Google Scholar
  120. 120.
    Willadsen, P., & McKenna, R. V. (1991). Vaccination with ―concealed antigens: Myth or reality? Parasite Immunology, 13, 605–616.PubMedCrossRefGoogle Scholar
  121. 121.
    Mans, B. J., Andersen, J. F., Schwan, T. G., & Ribeiro, J. M. (2008). Characterization of anti-hemostatic factors in the argasid, Argas monolakensis: Implications for the evolution of blood-feeding in the soft tick family. Insect Biochemisry and Molecular Biology, 38, 22–41.CrossRefGoogle Scholar
  122. 122.
    Gillespie, R. D., Dolan, M. C., Piesman, J., & Titus, R. G. (2001). Identification of an IL-2 binding protein in the saliva of the Lyme disease vector tick, Ixodes scapularis. Journal of Immunology, 166, 4319–4326.CrossRefGoogle Scholar
  123. 123.
    Francischetti, I. M., Mans, B. J., Meng, Z., Gudderra, N., Veenstra, T. D., Pham, V. M., & Ribeiro, J. M. (2008). An insight into the sialome of the soft tick, Ornithodoros parkeri. Insect Biochemisry and Molecular Biology, 38, 1–21.CrossRefGoogle Scholar
  124. 124.
    Leboulle, G., Crippa, M., Decrem, Y., Mejri, N., Brossard, M., Bollen, A., et al. (2002). Characterization of a novel salivary immunosuppressive protein from Ixodes ricinus ticks. Journal of Biological Chemistry, 277, 10083–10089.PubMedCrossRefGoogle Scholar
  125. 125.
    Andrade, B. B., Teixeira, C. R., Barral, A., & Barral-Netto, M. (2005). Haematophagous arthropod saliva and host defense system: At ale of tear and blood. Anais da Academia Brasileira de Ciências, 77, 665–693.PubMedCrossRefGoogle Scholar
  126. 126.
    Hajnická, V., Vancová, I., Kocáková, P., Slovák, M., Gašperík, J., Sláviková, M., et al. (2005). Manipulation of host cytokine network by ticks: A potential gateway for pathogen transmission. Parasitology, 130, 333–342.PubMedCrossRefGoogle Scholar
  127. 127.
    Ferreira, B. R., & Silva, J. S. (1999). Successive tick infestations selectively promote a T-helper2 cytokine profile in mice. Immunology, 96, 434–439.PubMedPubMedCentralCrossRefGoogle Scholar
  128. 128.
    Mejri, N., Franscini, N., Rutti, B., & Brossard, M. (2001). Th2 polarization of the immune response of Balb/c mice to Ixodes ricinus instars importance of several antigens in activation of specific Th2 sub populations. Parasite Immunology, 23, 61–69.PubMedCrossRefGoogle Scholar
  129. 129.
    Bergman, D. K., Palmer, M. J., Caimano, M. J., Radolf, J. D., & Wikel, S. K. (2000). Isolation and molecular cloning of a secreted immuno-suppressant protein from Dermacentor andersoni salivary gland. Journal of Parasitology, 86, 516–525.PubMedCrossRefGoogle Scholar
  130. 130.
    Kopecký, J., & Kuthejlová, M. (1998). Suppressive effect of Ixodes ricinus salivary gland extract on mechanisms of natural immunity in vitro. Parasite Immunology, 20, 169–174.PubMedGoogle Scholar
  131. 131.
    Ramachandra, R. N., & Wikel, S. K. (1992). Modulation of host-immune responses by ticks Acari: Ixodidae: Effects of salivary gland extracts on host macrophages and lymphocyte cytokine production. Journal of Medical Entomology, 5, 818–826.CrossRefGoogle Scholar
  132. 132.
    Cavassani, K. A., Aliberti, J. C., Dias, A. R., Silva, J. S., & Ferreira, B. R. (2005). Tick saliva inhibits differentiation maturation and function of murine bone marrow-derived dendritic cells. Immunology, 114, 235–245.PubMedPubMedCentralCrossRefGoogle Scholar
  133. 133.
    Ribeiro, J. M. C., & Mather, T. N. (1998). Ixodes scapularis: Salivary kininase activity is a metallo dipeptidyl carboxypeptidase. Experimental Parasitology, 89, 213–221.PubMedCrossRefGoogle Scholar
  134. 134.
    Paesen, G. C., Siebold, S., Harlos, K., Peacey, M. F., Nuttall, P. A., & Stuart, D. I. (2007). A tick protein with a modified Kunitz fold inhibits human tryptase. Journal of Molecular Biology, 368, 1172–1186.PubMedCrossRefGoogle Scholar
  135. 135.
    Daix, V., Schroeder, H., Praet, N., Georgin, J.-P., Chiappino, I., Gillet, L., et al. (2007). Ixodes ticks belonging to the Ixodes ricinus complex encode a family of anti-complement proteins. Insect Molecular Biology, 16, 155–166.PubMedCrossRefGoogle Scholar
  136. 136.
    Schoeler, G. B., & Wikel, S. K. (2001). Modulation of host immunity by haematophagous arthropods. Annals of Tropical Medicine and Parasitology, 95, 755–771.PubMedCrossRefGoogle Scholar
  137. 137.
    Wikel, S. K., & Alarcon-Chaidez, F. J. (2001). Progress toward molecular characterization of ectoparasite modulation of host immunity. Veterinary Parasitology, 101, 275–287.PubMedCrossRefGoogle Scholar
  138. 138.
    Garg, R., Juncadella, I. J., Ramamoorthi, N., Ashish Ananthanarayanan, S. K., Thomas, V., Rincón, M., et al. (2006). Cutting edge: CD4 is the receptor for the tick saliva immune-suppressor, Salp15. Journal of Immunology, 177, 6579–6583.CrossRefGoogle Scholar
  139. 139.
    Hajnicka, V., Fuchsberger, N., Slovak, M., Kocakova, P., Labuda, M., & Nutall, P. A. (1998). Tick salivary gland extracts promote virus growth in vitro. Parasitology, 116, 533–538.PubMedCrossRefGoogle Scholar
  140. 140.
    Shaw, M. K., Tilney, L. G., & Mckeever, D. J. (1993). Tick salivary gland extract and interleukin-2 stimulation enhances susceptibility of lymphocyte to infection by Theileria parva sporozoites. Infection and Immunity, 61, 1486–1495.PubMedPubMedCentralGoogle Scholar
  141. 141.
    Jones, L. D., Hodgson, E., & Nuttall, P. A. (1989). Enhancement of virus transmission by tick salivary glands. Journal of General Virology, 70, 1895–1898.PubMedCrossRefGoogle Scholar
  142. 142.
    Krocova, Z., Macela, A., Hernychova, L., Kroca, M., Pechova, J., & Kopecky, J. (2003). Tick salivary gland extract accelerates proliferation of Francisella tularensis in the host. Journal of Parasitology, 89, 14–20.PubMedCrossRefGoogle Scholar
  143. 143.
    Horká, H., Cerná-Kýcková, K., Skallová, A., & Kopecký, J. (2009). Tick saliva affects both proliferation and distribution of Borrelia burgdorferi spirochetes in mouse organs and increases transmission of spirochetes to ticks. International Journal of Medical Microbiology, 299, 373–380.PubMedCrossRefGoogle Scholar
  144. 144.
    Zeidner, N. S., Schneider, B. S., Nuncio, M. S., Gern, L., & Piesman, J. (2002). Coinoculation of Borrelia spp. with tick salivary gland lysate enhances spirochaete load in mice and is tick species-specific. Journal of Parasitology, 88, 1276–1278.PubMedGoogle Scholar
  145. 145.
    Krocová, Z., Macela, A., Hernychová, L., Kroca, M., Pechová, J., & Kopecký, J. (2003). Tick salivary gland extract accelerates proliferation of Francisella tularensis in the host. Journal of Parasitology, 89, 14–20.PubMedCrossRefGoogle Scholar
  146. 146.
    Ramamoorthi, N., Narasimhan, S., Pal, U., Bao, F., Yang, X. F., Fish, D., et al. (2005). The Lyme disease agent exploits a tick protein to infect the mammalian host. Nature, 436, 573–577.PubMedPubMedCentralCrossRefGoogle Scholar
  147. 147.
    Labuda, M., Nuttall, P. A., Kozuch, O., Eleckova, E., Williams, T., Zuffova, E., et al. (1993). Non viraemic transmission of tick-borne encephalitis virus: a mechanism for arbovirus survival in nature. Experientia, 49, 802–805.PubMedCrossRefGoogle Scholar
  148. 148.
    Richter, D., Allgöwer, R., & Matuschka, F. R. (2002). Co-feeding transmission and its contribution to the perpetuation of the Lyme disease spirochete Borrelia afzelii. Emerging Infectious Diseases, 8, 1421–1425.PubMedPubMedCentralCrossRefGoogle Scholar
  149. 149.
    Gern, L., & Rais, O. (1996). Efficient transmission of Borrelia burgdorferi between cofeeding Ixodes ricinus ticks (Acari: Ixodidae). Journal of Medical Entomology, 33, 189–192.PubMedCrossRefGoogle Scholar
  150. 150.
    Piesman, J., & Happ, C. M. (2001). The efficacy of co-feeding as a means of maintaining Borrelia burgdorferi: A North American model system. Journal of Vector Ecology, 26, 216–220.PubMedGoogle Scholar
  151. 151.
    Fialová, A., Cimburek, Z., Iezzi, G., & Kopecký, J. (2010). Ixodes ricinus tick saliva modulates tick-borne encephalitis virus infection of dendritic cells. Microbes and Infection, 12, 580–585.PubMedCrossRefGoogle Scholar
  152. 152.
    Severinová, J., Salát, J., Krocová, Z., Reznícková, J., Demová, H., Horká, H., et al. (2005). Co-inoculation of Borrelia afzelii with tick salivary gland extract influences distribution of immune competent cells in the skin and lymph nodes of mice. Folia Microbiologica, 50, 457–463.PubMedCrossRefGoogle Scholar
  153. 153.
    Lieskovská, J., & Kopecký, J. (2012). Tick saliva suppresses IFN signalling in dendritic cells upon Borrelia afzelii infection. Parasite Immunology, 34, 32–39.PubMedCrossRefGoogle Scholar
  154. 154.
    Lieskovská, J., & Kopecký, J. (2012). Effect of tick saliva on signalling pathways activated by TLR-2 ligand and Borrelia afzelii in dendritic cells. Parasite Immunology, 34, 421–429.PubMedCrossRefGoogle Scholar
  155. 155.
    Slámová, M., Skallová, A., Páleníková, J., & Kopecký, J. (2011). Effect of tick saliva on immune interactions between Borrelia afzelii and murine dendritic cells. Parasite Immunology, 33, 654–660.PubMedCrossRefGoogle Scholar
  156. 156.
    Kern, A., Collin, E., Barthel, C., Michel, C., Jaulhac, B., & Boulanger, N. (2011). Tick saliva represses innate immunity and cutaneous inflammation in a murine model of Lyme disease. Vector Borne Zoonotic Diseases, 11, 1343–1350.PubMedCrossRefGoogle Scholar
  157. 157.
    Hannier, S., Liversidge, J., Sternberg, J. M., & Bowman, A. S. (2003). Ixodes ricinus tick salivary gland extract inhibits IL-10 secretion and CD69 expression by mitogen- stimulated murine splenocytes and induces hypo-responsiveness in B lymphocytes. Parasite Immunology, 25, 27–37.PubMedCrossRefGoogle Scholar
  158. 158.
    Hovius, J. W., Schuijt, T. J., deGroot, K. A., Roelofs, J. J. T. H., Oei, A., Marquart, J. A., et al. (2008). Preferential protection of Borrelia burgdorferi sensu stricto by a Salp15 homologue in Ixodes ricinus saliva. Journal of Infectious Diseases, 198, 1189–1197.PubMedPubMedCentralCrossRefGoogle Scholar
  159. 159.
    Narasimhan, S., Sukumaran, B., Bozdogan, U., Thomas, V., Liang, X., DePonte, K., et al. (2007). A tick anti-oxidant facilitates the Lyme disease agent’s successful migration from the mammalian host to the arthropod vector. Cell Host & Microbe, 2, 7–18.CrossRefGoogle Scholar
  160. 160.
    Schuijt, T. J., Coumou, J., Narasimhan, S., Dai, J., Deponte, K., Wouters, D., et al. (2011). A tick mannose-binding lectin inhibitor interferes with the vertebrate complement cascade to enhance transmission of the Lyme disease agent. Cell Host & Microbe, 10, 136–146.CrossRefGoogle Scholar
  161. 161.
    Sukumaran, B., Narasimhan, S., Anderson, J. F., DePonte, K., Marcantonio, N., Krishnan, M. N., et al. (2006). An Ixodes scapularis protein required for survival of Anaplasma phagocytophilum in tick salivary glands. Journal of Experimental Medicine, 203, 1507–1517.PubMedPubMedCentralCrossRefGoogle Scholar
  162. 162.
    Labuda, M., Jones, L. D., Williams, T., & Nuttall, P. A. (1993). Enhancement of tick-borne encephalitis virus transmission by tick salivary gland extract. Medical and Veterinary Entomology, 7, 193–196.PubMedCrossRefGoogle Scholar
  163. 163.
    Pechova, J., Stepanova, G., Kovar, L., & Kopecky, J. (2002). Tick salivary gland extract-activated transmission of Borrelia afzelii spirochaetes. Folia Parasitologica (Praha), 49, 153–159.CrossRefGoogle Scholar
  164. 164.
    Kazimírová, M., Jancinová, V., Petríková, M., Takáè, P., Labuda, M., & Nosál, R. (2002). An inhibitor of thrombin stimulated blood platelet aggregation from the salivary glands of the hard tick Amblyomma variegatum (Acari: Ixodidae). Experimental and Applied Acarology, 28, 97–105.PubMedCrossRefGoogle Scholar
  165. 165.
    Sangamnatdej, S., Paesen, G. C., Slovak, M., & Nutall, P. A. (2002). A high affinity serotonin- and histamine binding lipocalin from tick saliva. Insect Molecular Biology, 11, 79–86.PubMedCrossRefGoogle Scholar
  166. 166.
    Mejri, N., Rutti, B., & Brossard, M. (2002). Immunosuppressive effects of Ixodes ricinus tick saliva or salivary gland extracts on innate and acquired immune response of BALB/c mice. Parasitology Research, 88, 192–197.PubMedCrossRefGoogle Scholar

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© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.Laboratory of Veterinary Microbiology and Epidemiology, Service of Medical Entomology, Institute Pasteur of TunisUniversity of Tunis El-ManarTunisTunisia

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