Ticks and tick-borne pathogens at the cutaneous interface: Host defenses, tick countermeasures, and a suitable environment for pathogen establishment

Frontiers in Microbiology

Volumn 4, Issue NOV, 2013, Pages

  Wikel, Stephen ^a  

^a New York   (United States)

Author keywords

Immune modulation; Immune response; Pathogen transmission; Skin; Tick saliva; Tick host interface; Ticks

Indexed keywords

ALPHA INTERFERON; BRADYKININ; CD83 ANTIGEN; CD86 ANTIGEN; CHEMOKINE; CYTOKINE; EOTAXIN; FIBROBLAST GROWTH FACTOR; HISTAMINE; INTERCELLULAR ADHESION MOLECULE 1; INTERLEUKIN 1; INTERLEUKIN 10; INTERLEUKIN 12; INTERLEUKIN 6; INTERLEUKIN 8; MACROPHAGE INFLAMMATORY PROTEIN 1BETA; PLATELET DERIVED GROWTH FACTOR; PROSTACYCLIN; PROSTAGLANDIN E2; RANTES; TRANSCRIPTOME; TRANSFORMING GROWTH FACTOR BETA; TUMOR NECROSIS FACTOR ALPHA; VASCULAR CELL ADHESION MOLECULE 1; VASODILATOR AGENT;

ADAPTIVE IMMUNITY; AMBLYOMMA VARIEGATUM; ARTICLE; CD4+ T LYMPHOCYTE; DERMACENTOR RETICULATUS; DISEASE TRANSMISSION; DOWN REGULATION; GENE EXPRESSION; HEMOSTASIS; HOST RESISTANCE; IMMUNE RESPONSE; IMMUNOMODULATION; INFLAMMATION; INNATE IMMUNITY; NONHUMAN; PRURITUS; RHIPICEPHALUS SANGUINEUS; SALIVA; SKIN MANIFESTATION; THROMBOCYTE AGGREGATION; TICK; TICK BITE; UPREGULATION; WOUND HEALING;

EID: 84890301042     PISSN: None     EISSN: 1664302X     Source Type: Journal    
DOI: 10.3389/fmicb.2013.00337     Document Type: Article

References (151)

1. Adams, T. S. (1999). Hematophagy and hormone release. Ann. Entomol. Soc. Am. 92, 1-13.
2. Alarcon-Chaidez, F. J., Boppana, V. D., Hagymasi, A. T., Adler, A. J., and Wikel, S. K. (2009). A novel sphingomyelinase-like enzyme present in tick saliva drives host CD4+ T cells to express IL-4. Parasite Immunol. 31, 210-219. doi: 10.1111/j.1365-3024.2009.01095.x.
3. Alarcon-Chaidez, F. J., Sun, J., and Wikel, S. K. (2007). Construction and characterization of a cDNA library from the salivary glands of Dermacentor andersoni stiles (Acari: Ixodidae). Insect Biochem. Mol. Biol. 37, 48-71. doi: 10.1016/j.ibmb.2006.10.002.
4. Alekseev, A. N., and Chunikhin, S. P. (1990). The experimental transmission of the tick-borne encephalitis virus by ixodid ticks (the mechanisms, time periods, species and sex differences). Parazitologiia 24, 177-185 (in Russian).
5. Alexander, J. O'D. (1986). The physiology of itch. Parasitol. Today 2, 345-351. doi: 10.1016/0169-4758(86)90055-4.
6. Allen, J. R. (1973). Tick resistance: basophils in skin reactions of resistant guinea pigs. Int. J. Parasitol. 3, 195-200. doi: 10.1016/0020-7519(73)90024-6.
7. Allen, J. R., Doube, B. M., and Kemp, D. H. (1977). Histology of bovine skin reactions to Ixodes holocyclus Neuman. Can. J. Comp. Med. 41, 26-35.
8. Allen, J. R., Khalil, H. M., and Graham, J. E. (1979). The location of tick salivary antigens, complement and immunoglobulin in the skin of guinea-pigs infested with Dermacentor andersoni. Immunology 38, 467-472.
9. Anderson, J. F., and Magnarelli, L. A. (2008). Biology of ticks. Infect. Dis. Clin. North Am. 22, 195-215. doi: 10.1016/j.idc.2007.12.006.
10. Anderson, J. M., and Valenzuela, J. G. (2008). "Tick saliva: from pharmacology and biochemistry to transcriptome analysis and functional genomics," in Ticks: Biology, Disease and Control, eds A. S. Bowman and P. A. Nuttall (Cambridge: Cambridge University Press), 92-107.
11. Barker, S. C., and Murrell, A. (2008). "Systematics and evolution of ticks with a list of valid genus and species names," in Ticks: Biology, Disease and Control, eds A. S. Bowman and P. A. Nuttall (Cambridge: Cambridge University Press), 1-39.
12. Beaufays, J., Adam, B., Mentsen-Dedoyart, C., Fievez, L., Grosjean, A., Decrem, Y., et al. (2008). Ir-LBP, an Ixodes ricinus tick salivary LTB4-binding lipocalin, interfers with host neutrophil function. PLoS ONE 3:e3987. doi: 10.1371/journal.pone.0003987.
13. Bell, J. F., Stewart, S. J., and Wikel, S. K. (1979). Resistance to tick-borne Francisella tularensis by tick-sensitized rabbits: allergic klendusity. Am. J. Trop. Med. Hyg. 28, 876-880.
14. Bergman, D. K., Palmer, M. J., Caimano, M. J., Radolf, J. D., and Wikel, S. K. (2000). Isolation and cloning of a secreted immunosuppressant protein from Dermacentor andersoni salivary gland. J. Parasitol. 86, 516-525.
15. Brossard, M., and Wikel, S. (2008). "Tick immunobiology," in Ticks: Biology, Disease and Control, eds A. S. Bowman and P. A. Nuttall (Cambridge: Cambridge University Press), 186-204.
16. Burke, G., Wikel, S. K., Spielman, A., Pollack, R., McKay, K., Krause, P. J., et al. (2005). Cutaneous tick hypersensitivity in humans is associated with decreased Lyme disease risk. Emerg. Infect. Dis. 11, 36-41. doi: 10.3201/eid1101.040303.
17. Campbell, J. J., Haraldsen, G., Pan, J., Rottman, J., Qin, S., Ponath, P., et al. (1999). The chemokine receptor CBR4 in vascular recognition by cutaneous but not intestinal memory T cells. Nature 400, 776-780. doi: 10.1038/23495.
18. Cavassani, K. A., Aliberti, J. C., Dias, R. V., Silva, J. S., and Ferreira, B. R. (2005). Tick saliva inhibits differentiation, maturation and function of murine bone-marrow-derived dendritic cells. Immunology 114, 235-245. doi: 10.1111/j.1365-2567.2004.02079.x.
19. Chen, G., Severo, M., Sohail, M., Sakhon, O. S., Wikel, S. K., Kotsyfakis, M., et al. (2012). Ixodes scapularis saliva mitigates inflammatory cytokine secretion during Anaplasma phagocytophilum stimulation of immune cells. Parasit. Vectors 5, 229. doi: 10.1186/1756-3305-5-229.
20. Chmelar, J., Calvo, E., Pedra, J. H. F., Francischetti, I. M. B., and Kotsyfakis, M. (2012). Tick salivary secretion as a source of antihemostatics. J. Proteomics 75, 3842-3854. doi: 10.1016/j.jprot.2012.04.026.
21. Christe, M., Rutti, B., and Brossard, M. (2000). Cytokines (IL-4 and IFN-γ and antibodies (IgE and IgG2a) produced in mice infected with Borrelia burgdorferi sensu stricto via nymphs of Ixodes ricinus ticks or syringe inoculations. Parasitol. Res. 86, 491-496. doi: 10.1007/s004360050699.
22. Clark, R. A. (2010). Skin-resident T cells: the ups and downs of on site immunity. J. Invest. Dermatol. 130, 362-370. doi: 10.1038/jid.2009.247.
23. Couvreur, B., Beaufays, J., Charon, C., Lahaye, K., Gensale, F., Denis, V., et al. (2008). Variability and action mechanism of a family of anticomplement proteins in Ixodes ricinus. PLoS ONE 3:e1400. doi: 10.1371/journal.pone.0001400.
24. Dai, J., Narasimhan, S., Zhang, L., Liu, L., Wang, P., and Fikrig, E. (2010). Tick histamine release factor is critical for Ixodes scapularis engorgement and transmission of Lyme disease agent. PLoS Pathog. 6:e1001205. doi: 10.1371/journal.ppat.1001205.
25. 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 anticomplement proteins. Insect Mol. Biol. 16, 155-166. doi: 10.1111/j.1365-2583.2006.00710.x.
26. 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 J. 275, 1485-1499. doi: 10.1111/j.1742-4658.2008.06308.x.
27. Dennis, D. T., and Piesman, J. F. (2005). "Overview of tick-borne infections of humans," in Tick-Borne Diseases of Humans, eds J. L. Goodman, D. T. Dennis, and D. E. Sonenshine (Washington, DC: American Society for Microbiology), 3-11.
28. Dinarello, C. A. (2007). Historical review of cytokines. Eur. J. Immunol. 37(Suppl. 1), S34-S45. doi: 10.1002/eji.200737772.
29. Deruaz, 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. J. Exp. Med. 205, 2019-2031. doi: 10.1084/jem.20072689.
30. de Taeye, S. W., Kreuk, L, van Dam, A. P., Hovius, J. W., and Schuijt, T. J. (2013). Complement evasion by Borrelia burgdorferi: it takes three to tango. Trends Parasitol. 29, 119-128. doi: 10.1016/j.pt.2012.12.001.
31. des Vignes, F., Piesman, J., Heffernan, R., Schulze, T. L., Stafford, K. C. III, and Fish, D. (2001). Effect of tick removal on transmission of Borrelia burgdorferi and Ehrlichia phagocytophila by Ixodes scapularis nymphs. J. Infect. Dis. 183, 773-778. doi: 10.1086/318818.
32. Fontaine, A., Diouf, I., Bakkali, N., Misse, D., Pages, F., Fusai, T., et al. (2011). Implications of haematophagous arthropod salivary proteins in host-vector interactions. Parasit. Vectors 4, 187. doi: 10.1186/1756-3305-4-187.
33. Francischetti, I. M. B. (2010). Platelet aggregation inhibitors from hematophagous animals. Toxicon 56, 1130-1144. doi: 10.1016/j.toxicon.2009.12.003.
34. Francischetti, I. M. B., Sa-Nunes, A., Mans, B. J., Santos, I. M., and Ribeiro, J. M. C. (2009). The role of saliva in tick feeding. Front. Biosci. 14:2051-2088. doi: 10.2741/3363.
35. Frischknecht, F. (2007). The skin as interface in the transmission of arthropod-borne pathogens. Cell. Microbiol. 9, 1630-1640. doi: 10.1111/j.1462-5822.2007.00955.x.
36. Fukumoto, S., Sakaguchi, T., You, M., Xuan, X., and Fujisaki, K. (2006). Tick troponin I-like molecule is a potent inhibitor for angiogenesis. Microvasc. Res. 71, 218-221. doi: 10.1016/j.mvr.2006.02.003.
37. Gillespie, R. D., Dolan, M. C., Piesman, J., and Titus, R. G. (2001). Identification of an IL-2 binding protein in the saliva of the Lyme disease vector tick, Ixodes scapularis. J. Immunol. 166, 4319-4327.
38. Gillespie, R. D., Mbow, M. L., and Titus, R. G. (2000). The immunomodulatory factors of blood feeding arthropod saliva. Parasite Immunol. 22, 319-331. doi: 10.1046/j.1365-3024.2000.00309.x.
39. Guo, X., Booth, C. J., Paley, M. A., Wang, X., DePonte, K., Fikrig, E., et al. (2009). Inhibition of neutrophil function by two tick salivary proteins. Infect. Immun. 77, 2320-2329. doi: 10.1128/IAI.01507-08.
40. Hajdusek, O., Sima, R., Ayllon, N., Jalovecka, M., Perner, J., de la Fuente, J., et al. (2013). Interaction of the tick immune system with transmitted pathogens. Front. Cell. Infect. Microbiol. 3:26. doi: 10.3389/fcimb.2013.00026.
41. Hajnická, V., Kocakova, P., Slovak, M., Labuda, M., Fuchsberger, N., and Nuttall, P. A. (2000). Inhibition of the antiviral action of interferon by tick salivary gland extract. Parasite Immunol. 22, 201-206. doi: 10.1046/j.1365-3024.2000.00296.x.
42. Hajnická, V., Kocáková, P., Sláviková, M., Slovák, M., Gašperik, J., Fuchsberger, N., et al. (2001). Anti-interleukin-8 activity of tick salivary gland extracts. Parasite Immunol. 23, 483-489. doi: 10.1046/j.1365-3024.2001.00403.x.
43. Hannier, S., Liversidge, J., Sternberg, J. M., and Bowman, A. S. (2003). Ixodes ricinus tick salivary gland extract inhibits IL-10 secretion and CD69 expression by mitogen-stimulated murine splenocytes and induces hyporesponsiveness in B lymphocytes. Parasite Immunol. 25, 27-37. doi: 10.1046/j.1365-3024.2003.00605.x.
44. Heinze, D. M., Wikel, S. K., Thangamani, S., and Alacron-Chaidez, F. J. (2012). Transcriptional profiling of the murine cutaneous response during initial and subsequent infestations with Ixodes scapularis nymphs. Parasit. Vectors 5, 26. doi: 10.1186/1756-3305-5-26.
45. Hellwage, J., Meri, T., Heikkila, T., Alitalo, A., Panelius, J., Lahdenne, P., et al. (2001). The complement regulator factor H binds to the surface protein OspE of Borrelia burgdorferi. J. Biol. Chem. 276, 8427-8435. doi: 10.1074/jbc.M007994200.
46. Hojgaard, A., Biketov, S. F., Shtannikov, A. V., Zeidner, N. S., and Piesman, J. (2009). Molecular identification of Salp15, a key salivary gland protein in the transmission of Lyme disease spirochetes, from Ixodes persulcatus and Ixodes pacificus (Acari: Ixodidae). J. Med. Entomol. 46, 1458-1463. doi: 10.1603/033.046.0631.
47. Horka, H., Cerna-Kyckova, K., Skallova, A., and Kopecky, J. (2009). Tick saliva affects both proliferation and distribution of Borrelia burgdorferi spirochetes in mouse organs and increases transmission of spirochetes to ticks. Int. J. Med. Microbiol. 299, 373-380. doi: 10.1016/j.ijmm.2008.10.009.
48. Hovius, J. W. R. (2009). Spitting image: tick saliva assists the causative agent of Lyme disease in evading host skin's innate immune response. J. Invest. Dermatol. 129, 2337-2339. doi: 10.1038/jid.2009.202.
49. Hovius, J. W., Ramamoorthi, N., Van't Veer, C., de Groot, K. A., Nijhof, A. M., Jongejan, F., et al. (2007). Identification of Salp15 homologues in Ixodes ricinus ticks. Vector Borne Zoonotic Dis. 7, 296-303. doi: 10.1089/vbz.2006.0624.
50. Hovius, J. W. R., de Jong, M. A. W. P., den Dunnen, J., Litjens, M., Fikrig, E., van der Poll, T., et al. (2008a). Salp 15 binding to DC-SIGN inhibits cytokine expression by impairing both nucleosome remodeling and RNA stabilization. PLoS Pathog. 4:e31. doi: 10.1371/journal.ppat.0040031.
51. Hovius, J. W., Schuijt, T. J., de Groot, K. A., Roelofs, J. J., Oei, G. A., Marquart, J. A., et al. (2008b). Preferential protection of Borrelia burgdorferi sensu stricto by a Salp15 homologue in Ixodes ricinus saliva. J. Infect. Dis. 198, 1189-1197. doi: 10.1086/591917.
52. Hunger, R. E., Sieling, P. A., Ochoa, M. T., Sugaya, M., Burdick, A. E., Rea, T. H., et al. (2004). Langerhans cells utilize CD1a and langerin to efficiently present nonpeptide antigens to T cells. J. Clin. Invest. 113, 701-708. doi: 10.1172/JCI200419655.
53. Ibrahim, M. A., Ghazy, A. H., Maharem, T. M., and Khalil, M. I. (2001). Factor Xa (Fxa) inhibitor from the nymphs of the camel tick Hyalomma dromedarii. Comp. Biochem. Physiol. B Biochem. Mol. Biol. 130, 501-512. doi: 10.1016/S1096-4959(01)00459-6.
54. 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 Pathog. 5:e1000497. doi: 10.1371/journal.ppat.1000497.
55. Jones, L. D., Hodgson, E., and Nuttall, P. A. (1989). Enhancement of virus transmission by tick salivary glands. J. Gen. Virol. 70, 1895-1898. doi: 10.1099/0022-1317-70-7-1895.
56. Jones, L. D., and Nuttall, P. A. (1990). The effect of host resistance to tick infestation on the transmission of Thogoto virus by ticks. J. Gen. Virol. 71, 1039-1043. doi: 10.1099/0022-1317-71-5-1039.
57. Jongejan, F., and Uilenberg, G. (2004). The global importance of ticks. Parasitology 129, S3-S14. doi: 10.1017/S0031182004005967.
58. Juncadella, I. J., and Anguita, J. (2009). The immunosuppressive tick salivary protein, Salp15. Adv. Exp. Med. Biol. 666, 121-131. doi: 10.1007/978-1-4419-1601-_10.
59. Kazimirova, M., and Stibraniova, I. (2013). Tick salivary compounds: their role in modulation of host defenses and pathogen transmission. Front. Cell. Infect. Microbiol. 3:43. doi: 10.3389/fcimb.2013.00043.
60. Kern, A., Collin, E., Barthel, C., Michel, C., Jaulhac, B., and Boulanger, N. (2011). Tick saliva represses innate immunity and cutaneous inflammation in a murine model of Lyme disease. Vector Borne Zoonotic Dis. 11, 1343-1350. doi: 10.1089/vbz.2010.0197.
61. Koh, C. Y., and Kini, R. M. (2009). Molecular diversity of anticoagulants from haematophagous animals. Thromb. Haemost. 102, 437-453. doi: 10.1160/TH09-04-0221.
62. Kopecky, J., and Kuthejlova, M. (1998). Suppressive effect of Ixodes ricinus salivary gland extract on mechanisms of natural immunity in vitro. Parasite Immunol. 20, 169-174.
63. Korn, T., Bettelli, E., Oukka, M., and Kuchroo, V. K. (2009). IL-17 and IL-17 cells. Annu. Rev. Immunol. 27, 485-517. doi: 10.1146/annurev.immunol.021908.132710.
64. Kotsyfakis, M., Horka, H., Salat, J., and Anderson, J. F. (2010). The crystal structures of two salivary cystatins from the tick Ixodes scapularis and the effect of these inhibitors on the establishment of Borrelia burgdorferi infection in a murine model. Mol. Microbiol. 77, 456-470. doi: 10.1111/j.1365-2958.2010.07220.x.
65. Kotsyfakis, M., Sa-Nunes, A., Francischetti, I. M. B., Mather, T. N., Andersen, J. F., and Ribeiro, J. M. C. (2006). Antiinflammatory and immunosuppressive activity of sialostatin L, a salivary cystatin from the tick, Ixodes scapularis. J. Biol. Chem. 28, 26298-26307. doi: 10.1074/jbc.M513010200.
66. Kraiczy, P., Skerkea, C., Brade, V., and Zipfel, P. F. (2001). Further characterization of complement regulator acquiring surface proteins of Borrelia burgdorferi. Infect. Immun. 69, 7800-7809. doi: 10.1128/IAI.69.12.7800-7809.2001.
67. Kramer, C., Nahmias, Z., Norman, D. D., Mulvihill, T. A., Coons, L. B., and Cole, J. A. (2008). Dermacentor variabilis: regulation of fibroblast migration by tick salivary gland extract and saliva. Exp. Parasitol. 119, 391-397. doi: 10.1016/j.exppara.2008.04.005.
68. Krause, P. J., Grant-Kels, J. M., Tahan, S. R., Dardick, K. R., Alarcon-Chaidez, F., Bouchard, K., et al. (2009). Dermatologic changes induced by repeated Ixodes scapularis bites and implications for prevention of tick-borne infection. Vector Borne Zoonotic Dis. 9, 603-610. doi: 10.1089/vbz.2008.0091.
69. Krocova, Z., Macela, A., Hernychova, L., Kroca, M., Pechova, J., and Kopecky, J. (2003). Tick salivary gland extract accelerates proliferation of Francisella tularensis in the host. J. Parasitol. 89, 14-20. doi: 10.1645/0022-3395(2003)089[0014:TSGEAP]2.0.CO;2.
70. Kubes, M., Fuchsberger, N., Labuda, M., Zuffova, E., and Nuttall, P. A. (1994). Salivary gland extracts of partially fed Dermacentor reticulatus ticks decrease natural killer cell activity in vitro. Immunology 82, 113-116.
71. Kubes, M., Kocakova, P., Slovak, M., Slavikova, M., Fuchsberger, N., and Nuttall, P. A. (2002). Heterogeneity in the effect of different Ixodid tick species on human natural killer cell activity. Parasite Immunol. 24, 23-28. doi: 10.1046/j.0141-9838.2001.00434.x.
72. Kupper, T. S., and Fuhlbrigge, R. C. (2004). Immune surveillance in the skin: mechanisms and clinical consequences. Nat. Rev. Immunol. 4, 211-222. doi: 10.1038/nri1310.
73. Labuda, M., Jones, L. D., Williams, T., and Nuttall, P. A. (1993). Enhancement of tick-borne encephalitis virus transmission by tick salivary gland extracts. Med. Vet. Entomol. 7, 193-196. doi: 10.1111/j.1365-2915.1993.tb00674.x.
74. Lawrie, C. H., Randolph, S. E., and Nuttall, P. A. (1999). Ixodes ticks: serum species sensitivity of anticomplement activity. Exp. Parasitol. 93, 207-214. doi: 10.1006/expr.1999.4456.
75. 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. J. Biol. Chem. 277, 10083-10089. doi: 10.1074/jbc.M111391200.
76. Lieskovska, J., and Kopecky, J. (2012). Tick saliva suppresses IFN signalling in dendritic cells upon Borrelia afzelii infection. Parasite Immunol. 34, 32-39. doi: 10.1111/j.1365-3024.2011.01345.x.
77. Machackova, M., Obornik, M., and Kopecky, J. (2006). Effect of salivary gland extract from Ixodes ricinus ticks on the proliferation of Borrelia burgdorferi sensu stricto in vivo. Folia Parasitol. 53, 153-158.
78. Mans, B. J. (2011). Evolution of vertebrate hemostatic and inflammatory control mechanisms in blood-feeding arthropods. J. Innate Immun. 3, 41-51. doi: 10.1159/000321599.
79. Mans, B. J., Anderson, J. F., Francischetti, I. M. B., Valenzuela, J. G., Schwan, T. G., Pham, V. M., et al. (2008). Comparative sialomics between hard and soft ticks: implications for the evolution of blood-feeding behavior. Insect Biochem. Mol. Biol. 38, 42-58. doi: 10.1016/j.ibmb.2007.09.003.
80. Martinon, F., Mayor, A., and Tschopp, J. (2009). The inflammasomes: guardians of the body. Annu. Rev. Immunol. 27, 229-265. doi: 10.1146/annurev.immunol.021908.132715.
81. Maxwell, S. S., Stoklasek, T. A., Dash, Y., Macaluso, K. R., and Wikel, S. K. (2005). Tick modulation of the in vitro expression of adhesion molecules by skin-derived endothelial cells. Ann. Trop. Med. Parasitol. 99, 661-672. doi: 10.1179/136485905X51490.
82. Merad, M., Ginhoux, F., and Collin, M. (2008). Origin homeostasis and function of Langerhans cells and other langerin-expressing dendritic cells. Nat. Rev. Immunol. 8, 935-947. doi: 10.1038/nri2455.
83. Moorhouse, D. E. (1969). "The attachment of some ixodid ticks to their natural hosts, in Proceedings of the Second International Congress of Acarology. Budapest, Hungary: Hungarian Academy of Sciences, 319-327.
84. 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 Mol. Biol. 11, 641-650. doi: 10.1046/j.1365-2583.2002.00375.x.
85. Nazario, S., Das, S., de Silva, A. M., Deponte, K., Marcantonio, N., Anderson, J. F., et al. (1998). Prevention of Borrelia burgdorferi transmission in guinea pigs by tick immunity. Am. J. Trop. Med. Hyg. 58, 780-785.
86. Neelakanta, G., Sultana, H., Fish, D., Anderson, J., and Fikrig, E. (2010). Anaplasma phagocytophilum induces Ixodes scapularis ticks to express an antifreeze glycoprotein gene that enhances their survival in the cold. J. Clin. Invest. 120, 3179-3190. doi: 10.1172/JCI42868.
87. Nestle, F. O., Di Meglio, P., Qin, J.-Z., and Nickoloff, B. J. (2009). Skin immune sentinels in health and disease. Nat. Rev. Immunol. 9, 679-691.
88. Nithiuthai, S., and Allen, J. R. (1985). Langerhans cells present tick antigens to lymph node cells from tick-sensitized guinea-pigs. Immunology 55, 157-163.
89. 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. J. Immunol. 174, 2084-2091.
90. Nuttall, P., and Labuda, M. (2008). "Saliva-assisted transmission of tick-borne pathogens," in Ticks: Biology, Disease and Control, eds A. S. Bowman and P. A. Nuttall (Cambridge: Cambridge University Press), 205-219.
91. Oliveira, C. J. F., Carvalho, W. A., Garcia, G. R., Gutierrez, F. R. S., de Miranda Santos, I. K. F., Silva, J. S., et al. (2010). Tick saliva induces regulatory dendritic cells: MAP-kinases and Toll-like receptor-2 expression as potential targets. Vet. Parasitol. 167, 288-297. doi: 10.1016/j.vetpar.2009.09.031.
92. Oliveira, C. J. F., Cavassani, K. A., More, D. D., Garlet, G. P., Aliberti, J. C., Silva, J. S., et al. (2008). Tick saliva inhibits the chemotactic function of MIP-1α and selectively impairs chemotaxis of immature dendritic cells by down-regulating cell-surface CCR5. Int. J. Parasitol. 38, 705-716. doi: 10.1016/j.ijpara.2007.10.006.
93. Oliveira, C. J. F., Sa-Nunes, A., Francischetti, I. M. B., Carregaro, V., Anatriello, E., Silva, J. S., et al. (2011). Deconstructing tick saliva: non-protein molecules with potent immunomodulatory properties. J. Biol. Chem. 286, 10960-10969. doi: 10.1074/jbc.M110.205047.
94. Paesen, G. C., Adams, P. L., Harlos, K., Nuttall, P. A., and Stuart, D. I. (2000). Tick histamine-binding proteins: lipocalins with a second binding cavity. Biochem. Biophys. Acta 1482, 92-101. doi: 10.1016/S0167-4838(00)00168-0.
95. Pechová, J., Kopecky, L., and Salát, J. (2004). Effect of tick salivary gland extract on the cytokine production by mouse epidermal cells. Folia Parasitol. 51, 367-372.
96. Pestka, S., Krause, C. D., Sarkar, D., Walter, M. R., Shi, Y., and Fisher, P. B. (2004). Interleukin-10 and related cytokines and receptors. Annu. Rev. Immunol. 22, 929-979. doi: 10.1146/annurev.immunol.22.012703.104622.
97. Peterkova, K., Vancova, I., Hajnicka, V., Slovak, M., Simo, L., and Nuttall, P. A. (2008). Immunomodulatory arsenal of nymphal ticks. Med. Vet. Entomol. 22, 167-171. doi: 10.1111/j.1365-2915.2008.00726.x.
98. Preston, S., Majtan, J., Kouremenou, C., Rysnik, O., Burger, L. F., Cruz, A. C., et al. (2013). Novel immunomodulators from hard ticks selectively reprogramme human dendritic cell responses. PLoS Pathog. 9:e1003450. doi: 10.1371/journal.ppat.1003450.
99. Prevot, P. P., Beschin, A., Lins, L., Beaufays, J., Grosjean, A., Bruys, L., et al. (2009). Exosites mediate the anti-inflammatory effects of a multifunctional serpin from the saliva of the tick Ixodes ricinus. FEBS J. 276, 3235-3246. doi: 10.1111/j.1742-4658.2009.07038.x.
100. Ramachandra, R. N., and Wikel, S. K. (1992). Modulation of host immune responses by ticks (Acari: Ixodidae): impact of salivary gland extracts on host macrophage and lymphocyte cytokine production. J. Med. Entomol. 29, 818-826.
101. 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. doi: 10.1038/nature03812.
102. Randolph, S. E. (2010). To what extent has climate change contributed to the recent epidemiology of tick-borne diseases? Vet. Parasitol. 167, 92-94. doi: 10.1016/j.vetpar.2009.09.011.
103. Ribeiro, J., Alarcon-Chaidez, F., Francischetti, I. M. B., Mans, B., Mather, T. N., Valenzuela, J. G., et al. (2006). An annotated catalog of salivary gland transcripts from Ixodes scapularis ticks. Insect Biochem. Mol. Biol. 36, 111-129. doi: 10.1016/j.ibmb.2005.11.005.
104. Ribeiro, J. M. C. (1987). Ixodes dammini: salivary anti-complement activity. Exp. Parasitol. 64, 347-353. doi: 10.1016/0014-4894(87)90046-4.
105. Ribeiro, J. M. C. (1995). How ticks make a living. Parasitol. Today 11, 91-93. doi: 10.1016/0169-4758(95)80162-6.
106. Ribeiro, J. M. C., Evans, P. M., McSwain, J. L., and Sauer, J. (1992). Amblyomma americanum: characterization of salivary prostaglandins E2 and F2 by RP-HPLC/bioassay and gas chromatography-mass spectrometry. Exp. Parasitol. 74, 112-116. doi: 10.1016/0014-4894(92)90145-Z.
107. Ribeiro, J. M. C., and Francischetti, I. M. B. (2003). Role of arthropod saliva in blood feeding: sialome and post-sialome perspectives. Annu. Rev. Entomol. 48, 73-88. doi: 10.1146/annurev.ento.48.060402.102812.
108. Ribeiro, J. M. C., Makoul, G. T., and Robinson, D. R. (1988). Ixodes dammini: evidence for salivary prostacyclin secretion. J. Parasitol. 74, 1068-1069. doi: 10.2307/3282240.
109. Ribeiro, J. M. C., and Mather, T. N. (1998). Ixodes scapularis: salivary kininase activity is a metallo dipeptidyl carboxypeptidase. Exp. Parasitol. 89, 213-221. doi: 10.1006/expr.1998.4296.
110. Ribeiro, J. M. C., and Spielman, A. (1986). Ixodes dammini: salivary anaphylatoxin inactivating activity. Exp. Parasitol. 62, 292-297. doi: 10.1016/0014-4894(86)90034-2.
111. Ribeiro, J. M. C., Weis, J. J., and Telford, S. R. III. (1990). Saliva of the tick Ixodes dammini inhibits neutrophil function. Exp. Parasitol. 70, 382-388. doi: 10.1016/0014-4894(90)90121-R.
112. Ricklin, D., Hajishengallis, G., Yang, K., and Lambris, J. D. (2010). Complement: a key system for immune surveillance and homeostasis. Nat. Immunol. 11, 785-797. doi: 10.1038/ni.1923.
113. Riek, R. F. (1962). Studies on the reactions of animals to infestation with ticks. VI. Resistance of cattle to infestation with the tick, Boophilus microplus (Canestrini). Aust. J. Agric. Res. 13, 532-550. doi: 10.1071/AR9620532.
114. Sallusto, F., and Baggiolini, M. (2008). Chemokines and leukocyte traffic. Nat. Immunol. 9, 949-952. doi: 10.1038/ni.f.214.
115. Sá-Nunes, A., Bafica, A., Lucas, D. A., Conrads, T. P., Veenstra, T. D., Andersen, J. F., et al. (2007). Prostaglandin E2 is a major inhibitor of dendritic cell maturation and function in Ixodes scapularis saliva. J. Immunol. 179, 1497-1505.
116. Schmelz, M. (2002). Itch-mediators and mechanisms. J. Dermatol. Sci. 28, 91-96. doi: 10.1016/S0923-1811(01)00167-0.
117. Schmelz, M. (2010). Itch and pain. Neurosci. Biobehav. Rev. 34, 171-176. doi: 10.1016/j.neubiorev.2008.12.004.
118. Schoeler, G. B., Manweiler, S. A., and Wikel, S. K. (1999). Ixodes scapularis: effects of repeated infestations with pathogen-free nymphs on macrophage and T lymphocyte cytokine responses of BALB/c and C3H/HeN mice. Exp. Parasitol. 92, 239-248. doi: 10.1006/expr.1999.4426.
119. Schoeler, G. B., and Wikel, S. K. (2001). Modulation of host immunity by haematophagous arthropods. Ann. Trop. Med. Parasitol. 95, 755-771. doi: 10.1080/0003498012011118.
120. 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. doi: 10.1161/CIRCULATIONAHA.113.003191.
121. Schuijt, T. J., Coumou, J., Narasimhan, S., Dai, J., DePonte, K., Wouters, D., et al. (2011). A tick mannose-binding lectin inhibitor interfers with the vertebrate complement cascade to enhance transmission of the Lyme disease agent. Cell Host Microbe 10, 136-146. doi: 10.1016/j.chom.2011.06.010.
122. Severinová, J., Salát, J., Krocová, Z., Reznïcková, J., Demová, H., Horká, H., et al. (2005). Co-inoculation of Borrelia afzelii with tick salivary gland extract influences distribution of immunocompetent cells in the skin and lymph nodes of mice. Folia Microbiol. 50, 457-463. doi: 10.1007/BF02931430.
123. Shaw, M. K., Tilney, L. G., and McKeever, D. J. (1993). Tick salivary gland extract and interleukin-2 stimulation enhance susceptibility of lymphocytes to infection by Theileria parva sporozoites. Infect. Immun. 61, 1486-1495.
124. Shaw, T. J., and Martin, P. (2009). Wound repair at a glance. J. Cell. Sci. 122, 3209-3213. doi: 10.1242/jcs.031187.
125. Singh, S. K., and Girschick, J. (2004). Molecular survival strategies of the Lyme disease spirochete Borrelia burgdorferi. Lancet Infect. Dis. 4, 575-583. doi: 10.1016/S1473-3099(04)01132-6.
126. Slamova, M., Skallova, A., Palenikova, J., and Kopecky, J. (2011). Effect of tick saliva on immune interactions between Borrelia afzelii and murine dendritic cells. Parasite Immunol. 33, 654-660. doi: 10.1111/j.1365-3024.2011.01332.x.
127. Sokol, C. L., and Medzhitov, R. (2010). Emerging functions of basophils in protective and allergic immune responses. Mucosal Immunol. 3, 129-137. doi: 10.1038/mi.2009.137.
128. Steen, N. A., Barker, S. C., and Alewood, P. F. (2006). Proteins in the saliva of the Ixodidae (ticks): pharmacological features and biological significance. Toxicon 47, 1-20. doi: 10.1016/j.toxicon.2005.09.010.
129. Stevenson, B., El-Hage, N., Hines, M. A., Miller, J. C., and Babb, K. (2002). Differential binding of host complement inhibitor factor H by Borrelia burgdorferi Erp surface proteins: a possible mechanism underlying the expansive host range of Lyme disease spirochetes. Infect. Immun. 70, 491-497. doi: 10.1128/IAI.70.2.491-497.2002.
130. Stibraniova, I., Lahova, M., and Bartikova, P. (2013). Immunomodulators in tick saliva and their benefits. Acta Virol. 57, 200-2016. doi: 10.4149/av_201_02_200.
131. Theilgaard-Monch, K., Knudsen, S., Follin, P., and Borregaard, N. (2004). The transcriptional activation program of human neutrophils in skin lesions supports their important role in wound healing. J. Immunol. 172, 7684-7693.
132. Theis, J. H., and Budwiser, P. D. (1974). Rhipicephalus sanguineus: sequential histopathology at the host-arthropod interface. Exp. Parasitol. 36, 77-105. doi: 10.1016/0014-4894(74)90115-5.
133. Trager, W. (1939). Acquired immunity to ticks. J. Parasitol. 25, 57-81. doi: 10.2307/3272160.
134. Tyson, K., Elkins, C., Patterson, H., Fikrig, E., and deSilva, A. (2007). Biochemical and functional characterization of Salp20, an Ixodes scapularis tick salivary protein that inhibits the complement pathway. Insect Mol. Biol. 16, 469-479. doi: 10.1111/j.1365-2583.2007.00742.x.
135. Valenzuela, J. G. (2004). Exploring tick saliva: from biochemistry to 'sialomes' and functional genomics. Parasitology 129, S83-S94. doi: 10.1017/S0031182004005189.
136. Valenzuela, J. G., Charlab, R., Mather, T. N., and Ribeiro, J. M. C. (2000). Purification, cloning, and expression of a novel salivary anticomplement protein from the tick, Ixodes scapularis. J. Biol. Chem. 275, 18717-18723. doi: 10.1074/jbc.M001486200.
137. Vancová, I., Hajincká, V., Slovák, M., and Nuttall, P. A. (2010). Anti-chemokine activities of ixodid ticks depend on tick species, developmental stage, and duration of feeding. Vet. Parasitol. 167, 274-278. doi: 10.1016/j.vetpar.2009.09.029.
138. Vancová, I., Slovák, M., Hajincká, V., Labuda, M., Simo, L., Peterlová, K., et al. (2007). Differential anti-chemokine activity of Amblyomma variegatum adult ticks during blood-feeding. Parasite Immunol. 29, 169-177. doi: 10.1111/j.1365-3024.2006.00931.x.
139. Vivier, E., Tomasello, E., Baratin, M., Walzer, T., and Ugolini, S. (2008). Functions of natural killer cells. Nat. Immunol. 9, 503-510. doi: 10.1038/ni1582.
140. Wada, T., Ishiwata, K., Koseki, H., Ishikura, T., Ugajin, T., Ohnuma, N., et al. (2010). Selective ablation of basophils in mice reveals their nonredundant role in acquired immunity against ticks. J. Clin. Invest. 120, 2867-2875. doi: 10.1172/JCI42680.
141. Wikel, S. K. (1979). Acquired resistance to ticks. Expression of resistance by C4-deficient guinea pigs. Am. J. Trop. Med. Hyg. 28, 586-590.
142. Wikel, S. K. (1982). Immune responses to arthropods and their products. Annu. Rev. Entomol. 27, 21-48. doi: 10.1146/annurev.en.27.010182.000321.
143. Wikel, S. K. (1996). Host immunity to ticks. Annu. Rev. Entomol. 41, 1-22. doi: 10.1146/annurev.en.41.010196.000245.
144. Wikel, S. K. (1999). Tick modulation of host immunity: an important factor in pathogen transmission. Int. J. Parasitol. 29, 851-859. doi: 10.1016/S0020-7519(99)00042-9.
145. Wikel, S. K., and Bergman, D. K. (1997). Tick-host immunology: significant advances and challenging opportunities. Parasitol. Today 13, 383-389. doi: 10.1016/S0169-4758(97)01126-5.
146. Wikel, S. K., Ramachandra, R. N., Bergman, D. K., Burkot, T. R., and Piesman, J. (1997). Infestation with pathogen-free nymphs of the tick Ixodes scapularis induces host resistance to transmission of Borrelia burgdorferi by ticks. Infect. Immun. 65, 335-338.
147. Willadsen, P. (1980). Immunity to ticks. Adv. Parasitol. 18, 293-311. doi: 10.1016/S0065-308X(08)60402-9.
148. Willadsen, P. (2008). "Anti-tick vaccines," in Ticks: Biology, Disease and Control, eds A. S. Bowman and P. A. Nuttall (Cambridge: Cambridge University Press), 424-446.
149. Wu, J., Wang, Y., Liu, H., Yang, H., Ma, D., Li, J., et al. (2010). Two immunoregulatory peptides with antioxidant activity from tick salivary glands. J. Biol. Chem. 285, 16606-16613. doi: 10.1074/jbc.M109.094615.
150. Zeidner, N., Dreitz, M., Belasso, D., and Fish, D. (1996). Suppression of acute Ixodes scapularis-induced Borrelia burgdorferi infection using tumor necrosis factor-alpha, interleukin-2, and interferon-gamma. J. Infect. Dis. 173, 187-195. doi: 10.1093/infdis/173.1.187.
151. Zeidner, N. S., Schneider, B. S., Nuncio, M. S., and Gern, L., and Piesman, J. (2002). Coinoculation of Borrelia spp. with tick salivary gland lysate enhances spirochete load in mice and is tick species-specific. J. Parasitol. 88, 1276-1278. doi: 10.1645/0022-3395.